Dimethylformamide → HCID 86585786, compound

HRID 278373Notes

Reaction equation

HRID 278373 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([C:7]([NH:9][C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[NH:12][CH:13]=[N:14]3)=[O:8])=[CH:5][CH:4]=1.CN(C=O)C.[H-].[Na+].[C:28]([O:32][C:33](=[O:36])[CH2:34]Br)([CH3:31])([CH3:30])[CH3:29]>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][N:14]3[CH2:34][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:36])=[O:8])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 9404764HCID 9404764, compound

Product 1

HCID 86585786HCID 86585786, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

After 27.03 g(0.20 mol) of adenine was dissolved in 500 ml of pyridine, 34.12 g(0.20 mol) of p-anisole chloride was added slowly over 55 minutes, and reacted for 4 hours at 100° C. with stirring. Then, the reaction temperature was lowered to room temperature, further reacted overnight with constant stirring, and removed pyridine by distilling under reduced vacuum. The resulting crude compound was recrystallized in isopropanol and methanol respectively, to give 33.7 g(0.13 mol) of white powder of N6-(4-methoxybenzoyl) adenine. 33.66 g(125 mmol) of N6-(4-methoxybenzoyl) adenine and 400 ml of DMF were placed in a 1 liter reaction flask, added 6.0 g(150 mmol) of 60% NaH slowly, added 22.15 ml(150 mmol) of t-butylbromoacetate in a dropwise over 1 hour 15 minutes, and then, reacted overnight. The reaction solvent, DMF was removed under reduced vacuum, and the precipitate was obtained after addition of water. The precipitate was separated and recrystallized in methanol to obtain 33.46 g(87.30 mmol) of N6-(4-methoxybenzoyl)-9-(t-butoxycarbonylmethyl) adenine as a white solid. In a 2 liter reaction flask, 33.46 g(87.30 mmol) of N6-(4-methoxybenzoyl)-9-(t-butoxycarbonylmethyl) adenine and 800 ml of dichloromethane were placed, mixed at room temperature, and added 180 ml of TFA. The reactants were mixed overnight at the same temperature with constant stirring. After dichloromethane and TFA were removed under reduced vacuum, the resulting crude compound was solubilized in 450 ml of 1N NaOH. The solution was washed with dichloromethane and acidified with 6N HCl to obtain 23.54 g(71.9 mmol) of N6-(4-methoxybenzoyl)-9-(carbonylmethyl) adenine as as white solid. In a 500 ml reaction flask, 21.99 g(67.20 mmol) of N6-(4-methoxybenzoyl)-9-(carbonylmethyl) adenine, 20.72 g(62.7 mmol) of benzyl N-[2-(t-butoxyl)aminoethyl]glycinate and 200 ml of dichloromethane were added sequentially, and then added 14.17 g(73.92 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiamide at once. The reaction mixture was incubated overnight at room temperature with constant stirring, extracted with dichloromethane and water, and washed with brine. The organic phase layer was dried with magnesium sulfate, and concentrated under reduced vacuum to obtain crude compound, which was subsequently purified through flash column chromatography by using a mobile phase of 5% methanol/dichloromethane to give 28.24 g(45.70 mol) of benzyl N-[2-(t-butoxylcarbonyl)aminoethyl]-N-[(N6-(4-methoxybenzoyl)-adenine-9-yl)acetyl]glycinate as a white powder. 400 ml of methanol was added to 28.24 g(45.70 mol) of the said compound, and then added 1.0 g of palladium on activated carbon(Pd/C) with stirring. Under hydrogen environment created by hydrogen balloon, the reaction flask was stirred for 3 hours. The catalyst was removed by filtering though celite, and evaporated the solvent under reduced vacuum. The resultant material was solubilized in 200 ml of 1N NaOH, washed with dichloromethane, acidified with 6N HCl and recrystallized in dichloromethane and hexane, respectively, to obtain 17.07 g(32.40 mmol) of N-[2-(t-butoxycarbonyl)aminoethyl]-N-[(N2-(4-methoxybenzoyl)-adenine-9-yl)acetyl]glycine(white powder) as a titled product.

Workup

  1. customreacted overnight
  2. customThe reaction solvent, DMF was removed under reduced vacuum
  3. customthe precipitate was obtained
  4. customThe precipitate was separated
  5. customrecrystallized in methanol

Sources & evidence

ORD record
ord-7f31e202f93f4ff19071b84a11bacd42
Source dataset
uspto-grants-2002_03
Patent number
US06359125B1

Reaction notes

Loading…