9-(2-Hydroxyethyl)adenine

In the 500 ml in the reaction bottle, adenine 37g (0.273 µM) suspended in acetonitrile 93 ml in, adding dioxolan 29.4g (0.334 µM), triethylamine 14.8g (0.146 µM) in N2 under protection 125 °C reaction 14h, slightly cold, pressure reducing recovery acetonitrile to obtain the solid particles, slightly cold, adds anhydrously ethanol 74 ml, heating to reflux and thermal insulation 1.5h, the ice-bath is cold to 0 °C under stirring 2h after-filtration, to obtain job filters the cake to dry 47.3g white powdery solid namely target product, yield 95percent.Example 5 The mechanical stirrer, reflux condenser and thermometer were installed in a 10 L reaction flask.To this, 3 kg (22.22 mol) of adenine, 2.14 kg (24.32 mol) of ethylene carbonate, 20 g (0.5 mol) of sodium hydroxide and 7 L of DMF were added thereto in turn, followed by stirring and heating under reflux for 4 hours.The reaction was terminated, cooled to room temperature, filtered, and the filter cake was dried under vacuum at 70 ° C for 6 hours.9-hydroxyethyl adenine as an off-white solid powder 3.29kg, Mp: 225 ~ 227 (decomposition), the yield of 82.7percent.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.In general, a mixture of alkylene carbonate (11.0 mmole), the heterocyclic base (10.0 mmole) and solid [NAOH] (0.5 mmol) in a solvent (e. g., DMA) (20 ml) was heated at [150°C] for 3 h. Then, the solvent was either evaporated and the residue taken up with a wash solvent, or diluted with a first solvent to precipitate the reaction products followed by a wash step with a wash solvent or wash solvent mixture (optionally followed by crystallization [FROMAPOS;A] crystallization solvent). Analysis of the reaction products was performed using HPLC and conditions as described in Figure 4, and a typical elution profile using such HPLC conditions is shown in Figure 5. Selected results of various reaction conditions, solvents, and wash/crystallization procedures are shown in Tables 1-3. For better visualization of the numerical differences in selectivity and yield, the following grayscale of Table A was used: Total Yield (in Shade Selectivity (as percent N9 alkylated percent) product) 50-64 Less than 76 65-74 77-83 r 75-84'i'84-87 88-90 a.. 3 _ s. 96-100 97-100 96-100, , , o 97_100 Table A Interestingly, as can be seen from Table 1 of Figure 1, when the solvent for dilution and crystallization was, or contained an aprotic and [APOLAR] solvent (here: toluene), and when DMF was used as a reaction solvent (and further depending on reaction temperature and workup), either the total yield was desirable at relatively undesirable selectivity, or the selectivity was desirable at relatively undesirable total yield. Replacement of the reaction solvent DMF with alternative solvents (shown here: DEF and DMA) appeared to improve the disparity between total yield and selectivity in a relatively unpredictable manner. Moreover, where the disparity between total yield and selectivity improved, total yields and selectivities were generally lower and frequently were at undesirable levels. After numerous further modifications (date not shown), the inventors eliminated the step of dilution of the reaction solvent by evaporation to force the reaction product from the solvent, and exemplary data on total yield and selectivity are shown in Table 2 of Figure 2. These data suggested that elimination of the dilution step tended to increase the total yield to at least some degree. However, improvement of the selectivity while maintaining relatively high total yields was inconsistent. In still further experiments, the inventors replaced the non-polar solvents for [DILUTION.] of the reaction solvent with relatively high polar solvents (IPA, ethyl acetate, acetonitrile, etc. ) when DMA was used as a reaction solvent. Surprisingly, and especially where DMA was the reaction solvent and IPA was the dilution and wash solvent, consistent high yields at high selectivity could be achieved under several reaction conditions as shown in the exemplary data on total yield and selectivity in Table 3 of Figure 3. Specifically, the total yield of product was as high as [91 percent] at an N9-alkylated product content of 97percent and an N7- alkylated byproduct content of 1.34percent (with [NAOH] as catalyst and 150 centigrade reaction temperature). Similarly, the total yield of product was as high as 87percent at an N9-alkylated product content of 97percent and an N7-alkylated byproduct content of 1.15percent (with [NAOH] as catalyst and 160 centigrade reaction temperature), and the total yield of product was as high as 82percent at a N9-alkylated product content of 98percent and a N7-alkylated byproduct content of 0.96percent (with [NAOH] as catalyst and 140 centigrade reaction temperature). Moreover, by using DMA as a reaction solvent various advantages other than higher total yield and an increase of selectivity may be achieved. Among other things, the solubility of various heterocyclic bases, and especially adenine, is significantly increased as shown in Table B below. Solvent Solubility at RT Solubility at 150°C DMF 2.90 m/ml 29. 0 mg/ml DEF 1. 36 mg/ml 13. 9 mg/ml DMA 4. 00 mg/ml 37.0 mg/ml [ TABLE B] Consequently, overall consumption of solvent may be significantly reduced by virtue of the increased solubility of the heterocyclic base in DMA (at least compared to DMF as reaction solvent), which in turn reduces the cost of preparing the alkylated heterocyclic base. Still further, due to the higher boiling point of DMA as compared to DMF (166.1 Centigrade as compared to 155 Centigrade, respectively) the reaction may be performed at a temperature that is further away from the boiling point of the reaction solvent, which increases the operational safety of the reaction. Moreover, while addition of a basic catalyst is generally not required, a basic catalyst, and preferably [NAOH] will benefit the total yield and selectivity.To a suspension of 60% NaH in mineral oil (1.70 g, 42.57 mmol) in anhydrous DMF (120 'iL) was added adenine (5.23 g, 38.70 mmol) under argon, and the mixture was heated at 600C for 1 h. 2-Bromoethylbenzoate (9.2 mL, 58.06 mmol) was added dropwise at 600C, and the reaction was stirred at this temperature for 16 h. The mixture was then filtered to remove insoluble materiel, the filtrate was evaporated under reduced pressure and co-evaporated three times with toluene. The residue was triturated with EtOAc then filtered to give a white solid, which was immediately resuspended in a saturated ammonia solution in MeOH (400 mL) . The reaction mixture was stirred for 14 h at room temperature, and then methanol was removed under reduced pressure. Recrystallization from EtOH afforded compound 2 (5.87 g, 85%): mp 236C (Lit. 238- 239C); 1H NMR (DMSO-d6) delta : 8.13 (s, IH, H-2), 8.10 (s, IH, H-8), 7.23 (bs, 2H, NH2), 5.05 (bs, IH, OH), 4.19 (t, J = 5.2 Hz, 2H, CH2O), 3.71 (t, J = 5.2 Hz, 2H, CH2N). 13C NMR (DMSO-d6) delta: 155.79, 152.23, 149.44, 141.46, 118.55, 59.17, 45.61. MS (GT, FAB+): 136 (B+1H) +, 180 (M+1H) +, 202 (M+Na)+.To a hot solution of A solution of 0.05 g (3.67 x 10-4 mol) of ZnCl2 in 10 mL ethanolwas added to a solution of 0.13 g (7.25 x 10-4 mol) of the ligand in 25 mL ethanol. The obtained solution was refluxed for 1 h. Afterseveral weeks, white crystals of (2) suitable for X-ray analysis wereobtained.FTIR spectral data (KBr disc, cm-1), Table 1.1H NMR (300 MHz, DMSO, d6): delta 3.73 (t, 2H, CH2O); 4.2 (t, 2H, NCH2); 5.068 (s, 1H, OH); 7.247 (s, 2H, NH2), 8.12 (s, 1H, C8-H); 8.15(s, 1H, C2-H).Anal. for C14H18ZnCl2N10O2, 494.65 g/mol.Calc. % C = 33.99, % H = 3.67, % N = 28.32; Found. % C = 34.02, %H = 3.76, % N = 28.04.A hot solution of 0.141 g (4.0 x 10-4 mol) of Co(acac)3 in 20 mLethanol was added dropwise to 0.10 g of the ligand

Molecular Weight:179.18
XLogP3:-0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:179.08070993
Monoisotopic Mass:179.08070993
Topological Polar Surface Area:89.8
Heavy Atom Count:13
Complexity:178
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes