5,7-Dimethoxy[1,2,4]triazolo[1,5-a]pyrimidin-2-amine

White solid

DryPowder

A solution of 3a (114.5 g, 0.4 mol) and hydroxylamine hydrochloride (40.3 g, 0.58 mol) in EtOH (600 mL) was stirred vigorously for 0.5 h at 60 C, then triethylamine (58.7 g, 0.58 mol) was added dropwise into the mixture. The resultant mixture was refluxed for 5 h, then cooling to the room temperature. The white solid product of4a was collected by filtration and washed using 200 mL water, yield 71.4 g (91.5percent);In 1000mL equipped with a stirrer, thermometer, reflux condenser, droppingfunnel, 4-neck flask, was added 600mL ethanol, N- (4, 6- dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea 114.5g (0.4mol), hydroxylamine hydrochloride 40.3g (0.58mol), heated to 60 , was added dropwise 58.7g (0.58mol) of triethylamine, 0.5H addition wascomplete, the reaction was refluxed 5H, until starting material N- ( after 4, 6-dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea reaction was complete, cooled toroom temperature filtration and dried 200mL, 50 water washing was stirred 20min, filtered dried to give the product 71.4 g, a purity of 98.6percent, a yield of about 91.5percent.2. One pot procedure for the synthesis of 2-amino-5, 7-dimethoxy [1, 2, 4] triazolopyrimidine (ADTP) from 2-amino-4, 6-dimethoxypyrimidine (ADP) 11. 9 g (0.075 mol) ADP was dissolved in 68 g ethyl acetate. 11 g (0.0825 mol) ethoxycarbonyl isothiocyanate was added within 20 min. at 78°C (no exotherm). The mixture was stirred over 5 h at reflux (78-79°C). 49.2 g (0.075 mol) hydroxylammonium sulfate (25 percent solution in water) were added and the mixture heated to 71°C (reflux aceotrope). 50 g (0.1 mol) diluted caustic soda (2 mot/1) was added within 1 h to establish the pH from 1.3 to 6.5 and hold at 6.5-7. 0 (offgas C02 and H2S, slightly exotherm). The mixture was stirred over 6 h under reflux (71°C) for reaction completion. The mixture was cooled down over night to 20°C. The product (ADTP) was filtrated and washed 3 times with each 25 g water to remove the salt (Na content after first wash 0.42 percent, after second 0.20 percent, after third 0.025 percent). Finally the solid ADTP was dried. Yield : 91.1 percent in respect to ADP, purity 95.3 percent (quantitative HPLC assay).A solution of 3a (114.5 g, 0.4 mol) and hydroxylamine hydrochloride (40.3 g, 0.58 mol) in EtOH (600 mL) was stirred vigorously for 0.5 h at 60 C, then triethylamine (58.7 g, 0.58 mol) was added dropwise into the mixture. The resultant mixture was refluxed for 5 h, then cooling to the room temperature. The white solid product of4a was collected by filtration and washed using 200 mL water, yield 71.4 g (91.5percent);In 1000mL equipped with a stirrer, thermometer, reflux condenser, droppingfunnel, 4-neck flask, was added 600mL ethanol, N- (4, 6- dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea 114.5g (0.4mol), hydroxylamine hydrochloride 40.3g (0.58mol), heated to 60 , was added dropwise 58.7g (0.58mol) of triethylamine, 0.5H addition wascomplete, the reaction was refluxed 5H, until starting material N- ( after 4, 6-dimethoxy-pyrimidin-2-yl) -N'-ethoxycarbonyl thiourea reaction was complete, cooled toroom temperature filtration and dried 200mL, 50 water washing was stirred 20min, filtered dried to give the product 71.4 g, a purity of 98.6percent, a yield of about 91.5percent.2. One pot procedure for the synthesis of 2-amino-5, 7-dimethoxy [1, 2, 4] triazolopyrimidine (ADTP) from 2-amino-4, 6-dimethoxypyrimidine (ADP) 11. 9 g (0.075 mol) ADP was dissolved in 68 g ethyl acetate. 11 g (0.0825 mol) ethoxycarbonyl isothiocyanate was added within 20 min. at 78°C (no exotherm). The mixture was stirred over 5 h at reflux (78-79°C). 49.2 g (0.075 mol) hydroxylammonium sulfate (25 percent solution in water) were added and the mixture heated to 71°C (reflux aceotrope). 50 g (0.1 mol) diluted caustic soda (2 mot/1) was added within 1 h to establish the pH from 1.3 to 6.5 and hold at 6.5-7. 0 (offgas C02 and H2S, slightly exotherm). The mixture was stirred over 6 h under reflux (71°C) for reaction completion. The mixture was cooled down over night to 20°C. The product (ADTP) was filtrated and washed 3 times with each 25 g water to remove the salt (Na content after first wash 0.42 percent, after second 0.20 percent, after third 0.025 percent). Finally the solid ADTP was dried. Yield : 91.1 percent in respect to ADP, purity 95.3 percent (quantitative HPLC assay).Ethyl [(4, 6-dimethoxypyrimidin-2-yl)amino carbonothioylcarbamate (0.50 g, 1.7 mmol) was mixed with ethanol (5 mL). To this mixture was added hydroxylamine hydrochloride (0.12 g, 1.7 mmol) and diisopropylethyl-amine (0.30 mL, 1.7 mmol). The resulting mixture was allowed to stir at room temperature. After 2.5 hours, additional diisopropylethylamine (0.30 mL, 1.7 mmol) was added to the mixture. After 48 hours the ethanol was removed in vacuo and the residue was partitioned between H2O and Et2O to give a powder. The powder was filtered and dried to afford the product as a tan powder (0.27 g, 82%). mp 215-220 C. Anal: Cacld for C7H9N5O2: C, 43.08; H, 4.65; N, 35.88; O, 16.39; found: C, 39.88; H, 4.22; N, 32.00; O, 16.35. 1H NMR (DMSO-d6): delta 6.04 (s, 1H); 5.97 (br, 2H); 4.04 (s, 3H).5) into the ring: to the third reactor into the second intermediate, caustic soda 250kg, hydroxylamine hydrochloride 100kg, 850kg acetonitrile, the reactor temperature maintained at 40 C for 12 hours, caustic soda and NaOH, water and NaOH Of the weight ratio of 1: 1; 6) filtration: After the reaction, the third reactor for material filtration, filtration of the liquid phase by distillation to recover acetonitrile 790kg; 7) Drying: The obtained solid phase was filtered and dried to obtain 198 kg of finished product.The compound 4a (6 g, 0.03 mol), catalytic amount of DMSO and3, 5-lutidine (9.6 g, 0.09 mol) were dissolved in MeCN (15 mL), and then 7c (10.3 g, 0.03 mol) was addedslowly with stirring at 35 C and keeping for 1 h. The reaction system was heated to 45 C and kept thatuntil the complete conversion monitoring by HPLC. Then the resultant mixture was slowly added into10% sulfuric acid aqueous solution (100 mL). After filtering, the residue was purified by recrystallizingfrom MeCN to afford white solid, yield 13.5 g (89.6%);A four-necked flask equipped with a stirrer, a thermometer, an air condenser and a dropping funnel was charged with 3, 5-lutidine 9.68 (0.0911101), acetonitrile 15, dimethyl sulfoxide 1, 2- A solution of 6-amino-5, 7-dimethoxy [1, 2, 4] triazolo [1, 5-a] pyrimidine 6g (0.03mIl) was added thereto. After sufficiently stirring for 10 minutes, 2- (tetrahydrofuryl -2-methoxy) -6-trifluoromethylbenzenesulfonyl chloride 10. 3g (0.03mol), control the temperature slowly increased to 33 ~ 35 C reaction lh, And then heated to 42 C reaction lh, to be raw materials 2-amino-5, 7-dimethoxy [1, 2, 4] triazolo [1, 5-a] pyrimidine reaction is completed, the cooling down The reaction solution was slowly added to 10% sulfuric acid water and stirred at 40 C for 0.5 h. The rate of 89. 6%, the nuclear magnetic resonance spectrum shown in Figure 1.General procedure: The compound 4a (6 g, 0.03 mol), catalytic amount of DMSO and3, 5-lutidine (9.6 g, 0.09 mol) were dissolved in MeCN (15 mL), and then 7c (10.3 g, 0.03 mol) was addedslowly with stirring at 35 C and keeping for 1 h. The reaction system was heated to 45 C and kept thatuntil the complete conversion monitoring by HPLC. Then the resultant mixture was slowly added into10% sulfuric acid aqueous solution (100 mL). After filtering, the residue was purified by recrystallizingfrom MeCN to afford white solid, yield 13.5 g (89.6%);General procedure: The compound 4a (6 g, 0.03 mol), catalytic amount of DMSO and3, 5-lutidine (9.6 g, 0.09 mol) were dissolved in MeCN (15 mL), and then 7c (10.3 g, 0.03 mol) was addedslowly with stirring at 35 C and keeping for 1 h. The reaction system was heated to 45 C and kept thatuntil the complete conversion monitoring by HPLC. Then the resultant mixture was slowly added into10% sulfuric acid aqueous solution (100 mL). After filtering, the residue was purified by recrystallizingfrom MeCN to afford white solid, yield 13.5 g (89.6%);3. Preparation of N-(5, 7-dimethoxy[1, 2, 4]triazolo-[1, 5-a]pyrimidin-2-yl)-2, 6-dichlorobenzene-sulfonamide (Compound 1) 2-Amino-5, 7-dimethoxy[1, 2, 4]triazolo[1, 5-a]-pyrimidine (0.75 g, 3.8 mmol) and 2, 6-dichlorobenzene-sulfonyl chloride (1.86 g, 7.6 mmol) were mixed in dry acetonitrile (15 mL). To this mixture was added dry pyridine (0.61 mL) and dry DMSO (54 muL, 0.7 mmol). The mixture was allowed to stir at room temperature. After 24 hours, the solvent was removed in vacuo, the residue was partitioned between CH2Cl2 (300 mL) and 2N HCl and the solids were collected by vacuum filtration to give a white solid A. The CH2Cl2 was dried (MgSO4) and removed in vacuo to give a white solid B. Both HPLC and NMR indicated that solid A and B are product. The solids were combined to afford the product as a white powder (1.41 g, 92%). mp 211-213 C. Anal: Cacld for C13H11Cl2N5O4S: C, 38.63; H, 2.74; N, 17.33; S, 7.93; found: C, 38.11; H, 2.68; N, 16.83; S, 7.77. 1H NMR (DMSO-d6): delta 12.4 (bs, 1H); 7.64-7.54 (m, 3H); 6.26 (s, 1H); 4.07 (s, 3H); 3.88 (s, 3H).

Agricultural chemicals (non-pesticidal)

Agricultural products (non-pesticidal)

25,000 - 100,000 lb

Molecular Weight:195.18
XLogP3:0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:2
Exact Mass:195.07562455
Monoisotopic Mass:195.07562455
Topological Polar Surface Area:87.6
Heavy Atom Count:14
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes