1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic

DOTA tert-Butyl ester is a benxyl derivative of the cyclic tosamide; can be nitrated directly; is more convenient to incorporate the nitro group after deprotection lithium aluminum hydride.

1, 4, 7, 10-Tetraazacyclododecane (1 g, 5.81 mmol) was dissolved in dry acetonitrile (20 ml) under nitrogen at 0(a) tert-butylbromoacetate, KIn a 500 ml round bottom flask, the compound (1) (2 g, 11.62 mmol) and sodium acetate (2.85 g, 34.8 mmol) were dissolved in N, N-dimethylacetamide (DMA, 25 mL). Tert-butyl bromoacetate (6.79 g, 34.82 mmol) was dissolved in N, N-dimethylacetamide (10 mL) at 0 ° C under ice-cooling, and reacted at room temperature for 5 days, After the completion of the reaction and then pour 125ml of water, then the reaction will be slightly yellow solution, And then slowly add sodium bicarbonate, will find the reaction of white precipitate produced, The precipitate was filtered and the precipitate was dissolved in 150 mL of chloroform, and washed with water (3 x 100 mL), discard the aqueous phase. The organic phase was dried over sodium sulfate (Na2SO4) and concentrated under reduced pressure. The organic phase was recrystallized from diethyl ether to give the compound (2) (4.1 g, 78percent) as a white solid. Having a structure of the following formula 3:3.3 equivalents of tert-butyl bromoacetate (773.0 mg, 7.6 mmol) dissolved in 10.0 mL anhydrous chloroform was added dropwise to a mixture of 1, 4, 7, 10-tetraazacyclododecane (cyclen) (400.0 mg, 2.32 mmol) and 10.0 equivalents of triethylamine (2.3 g, 23.2 mmol) in 40 mL anhydrous chloroform under an argon atmosphere for about half an hour. The reaction mixture was stirred for another 2 hours, and 0.5 equivalents of anhydrous K2CO3 was added. After a further 14 hours of reaction, the resulting solution was washed by water (3 x 40 mL). Then anhydrous Na2SO4 was used to dry the organic phase and the solvent was removed under vacuum to give a transparent oil. This crude product was purified by flash chromatography on aluminium oxide (dichloromethane/methane = 200: 5 (volume/volume), Rf = 0.35) to give tris-(tert-butoxycarbonylmethyl)-1, 4, 7, 10-tetraazacyclododecane (1) as a white powder (0.92 g, 1.78 mmol), yield: 77percent. mp 178-180°C, 1H NMR (400 MHz, CDCl3) : δ 3.34 (4H, s), 3.26 (214, s), 3.05 (4H, s), 2.89-2. 85 (12H, m), 1.47 (27H, s) ; 13C NMR (100 MHz, CDCl3) : δ 170.5 (2 x C), 169.6 (C), 81.6 (3 x C), 58.2 (3 x CH2), 51. 3 (2 x CH2), 51. 1 (2 x CH2) 49.2 (2 x CH2), 47.5 (2 x CH2) 28.2 (3 x CH3) ; ESIMS m/z 515.3 (M+H)+; HRFABMS m/z 515. 3811 (M+H)+ [Calcd. For C26H51N4O6(M+H)+, 515.3809].Example 1-Synthesis of Tri-tert-butyl 2, 2', 2'-(1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triyl)triacetate The protocol from O. Axelsson et al in WO200612723 2006 was used. Cyclen (1, 4, 7, 10-tetraazacyclododecane) (5.0 g, 29 mmol) and AcONa (7.22 g. 88 mmol) were introduced in dry DMA (80 mL) under argon, α-bromo-tert-butylacetate (13 mL, 87 mmol) dissolved in dry DMA (13 ml) was added drop by drop at 0 °C and the reaction was performed at room temperature during 5 days. At the end of the reaction, water (140 ml) was poured into the mixture and pH was adjusted at 9 with NaTo a suspension of cyclen (5.00 g, 29 mmol) and sodium acetate (7.86 g, 96 mmol) in DMA (60 mL) at -20 °C was added a solution of f-butyl bromoacetate (18.7 g, 14.1 mL, 96 mmol) in DMA (20 mL) dropwise over a period of 0.5 hour. The temperature was maintained at -20 °C during the addition, after which the reaction mixture was allowed to come to room temperature. After 24 hours of vigorous stirring, the reaction mixture was poured into water (300 mL) to give a clear solution. Solid KHCO3 (15 g, 1 50 mmol) was added portion wise, and compound 2 precipitated as a white solid. The precipitate was collected by filtration and dissolved in CHCI3 (250 mL). The solution was washed with water (100 mL), dried (MgSOA solution of 2.20 equivalents of tert-butylbromoacetate in CHClDissolve 2.0 g (11.6 mmol) starting material-1, 4, 7, 10-tetraazacyclododecane in 25 ml dimethylacetamide and add 2.85 g (34.7 mmol) sodium acetate into the solution. Take 2.0 grams (g), 11.6 millimol (mmol) of starting material 1, 4, 7, 10-tetraazacyclododecane (1, 4, 7, 10-tetraazacyclododecane) dissolved in 25 ml (ml) of dimethyl acetamidine In the case of dimethylacetamide, Then add 2.85 grams, 34.7 milliliters of sodium acetate, Placed in a 0 degree ice bath, Add 6.9 grams dropwise, 35.6 mmol of tert-butyl bromoacetate Moore (tert-butyl bromoacetate), Stir at room temperature for five days.Then, the aforementioned starting solution is poured into 125 ml of water.And add sodium bicarbonate in batches, After filtration, a solid is obtained.The above solid was dissolved in 150 ml of chloroform (Chloroform).And add 75 ml of water for cleaning.Next, take out the organic layer, Add anhydrous sodium sulfate to remove water, After concentration under reduced pressure, it was placed in 20 ml of chloroform.Recrystallization from 150 ml of ethanol, 3.83 g of a 64.0percent white solid product are obtained as 1, 4, 7-tris(tert-butoxycarbonylmethyl)-1, 4, 7, 10-tetraazacyclododecane.A solution of cyclen S1 (2.90 g, 16.83 mmol), NaHCOReaction of cyclen with 3.0 eq of tert-butyl bromoacetate: (0169) To a solution of cyclen 1 (500 mg, 2.9 mmol) in anhydrous CHCl3.5 equiv. of appropriate tert-Butyl bromoacetate (1.2 mL, 7.6 mmol) dissolved in 10.0 mL of anhydrous chloroform was added dropwise to a mixture of 1, 4, 7, 10-tetraazacyclododecane (cyclen) (400.0 mg, 2.32 mmol) and 10.0 equiv. triethylamine (2.3 g, 23.2 mmol) in 40 mL of anhydrous chloroform under NTo a solution of tert-butyl bromoacetate (8.67 g, 44.23 mmol) in dry MeCN (75 cmThis cyclen derivative was prepared according to the procedure described by O. Reany et al., J. Chem. Soc. Perkin. Trans 2., 2000, 1819. A mixture of cyclen (2.54 g, 14.7 mmol), te/t-butγl bromoacetate (8.67 g, 44.2 mmol) and NaHCOTo a mixture of 1, 4, 7, 10-tetraazacyclododecane (cyclen) (2.00 g, 11 mmol) and NaHCO

Molecular Weight:514.7
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:12
Exact Mass:514.37303533
Monoisotopic Mass:514.37303533
Topological Polar Surface Area:101
Heavy Atom Count:36
Complexity:665
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes