Diisopropylethylamine → 4-N-acetyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)cytidine

HRID 1694674

Reaction equation

HRID 1694674 reaction equation
[C:1]([NH:4][C:5]1[CH:42]=[CH:41][N:8]([C@@H:9]2[O:40][C@H:14]([CH2:15][O:16][C:17]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C@@H:12]([OH:13])[C@H:10]2[OH:11])[C:7](=[O:43])[N:6]=1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[C:53]([CH2:55][CH2:56][O:57][CH2:58]Cl)#[N:54].C(=O)(O)[O-].[Na+]>ClCCCl>[C:1]([NH:4][C:5]1[CH:42]=[CH:41][N:8]([C@@H:9]2[O:40][C@H:14]([CH2:15][O:16][C:17]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)[C@@H:12]([OH:13])[C@H:10]2[O:11][CH2:58][O:57][CH2:56][CH2:55][C:53]#[N:54])[C:7](=[O:43])[N:6]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10929984N-(1-((2R,3R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3,4-dihydroxytetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamideHCID 116654052-Cyanoethyl chloromethyl ether

Product 1

HCID 866307224-N-acetyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)cytidineYield 35%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

N4-Acetyl-5′-O-(4,4′-dimethoxytrityl)cytidine (588 mg, 1 mmol) was dissolved in 4 mL of 1,2-dichloroethane, and 452 mg of diisopropylethylamine (3.5 mmol) was added thereto, and then 365 mg of dibutylstannyl dichloride (1.2 mmol) was further added. The reaction was performed at room temperature for 1 hour. Then, the reaction was performed at 80° C., and 155.4 mg of chloromethyl 2-cyanoethyl ether (1.3 mmol) was added dropwise, and the solution was stirred for 60 minutes. After the reaction completed, the reaction solution was added into an aqueous saturated sodium bicarbonate solution, and was extracted with methylene chloride. The extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained mixture was purified by 30 g of silica gel column chromatography to obtain N4-acetyl-5′-O-(4,4′-dimethoxytrityl)-2′-O-(2-cyanoethoxymethyl) cytidine (219 mg, yield 35%).

Workup

  1. customwas performed at 80° C.
  2. extractionwas extracted with methylene chloride
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off
  5. customThe obtained mixture was purified by 30 g of silica gel column chromatography

Sources & evidence

ORD record
ord-43d9a27bf16a4ed081b46b9d34773886
Source dataset
uspto-grants-2012_04
Patent number
US08158775B2

Linked notes

Loading…