Acetic Anhydride → (S)-3-(2-amino-5-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-6-methylpyrimidin-4-ylamino)hexyl acetate

HRID 2207092Notes

Reaction equation

HRID 2207092 reaction equation
[C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].C(N(C(C)C)CC)(C)C.[NH2:17][C:18]1[N:23]=[C:22]([NH:24][C@@H:25]([CH2:29][CH2:30][CH3:31])CCO)[C:21]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])=[CH:35][C:34]=2[O:51][CH3:52])=[C:20]([CH3:53])[N:19]=1>CN(C)C1C=CN=CC=1.C1COCC1.O.C(OC([O-])=O)(O)=O.[Na+]>[C:5]([O:4][CH2:1][CH2:2][C@@H:25]([NH:24][C:22]1[C:21]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][CH2:42][O:43][Si:44]([C:47]([CH3:48])([CH3:49])[CH3:50])([CH3:46])[CH3:45])=[CH:35][C:34]=2[O:51][CH3:52])=[C:20]([CH3:53])[N:19]=[C:18]([NH2:17])[N:23]=1)[CH2:29][CH2:30][CH3:31])(=[O:7])[CH3:6]

Participants

8

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 131735875(S)-3-(2-amino-5-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-6-methylpyrimidin-4-ylamino)hexan-1-ol

Product 1

HCID 89907092(S)-3-(2-amino-5-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-6-methylpyrimidin-4-ylamino)hexyl acetate

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 88008498Sodium hydrogen dicarbonateSolvent

Procedure

4-Dimethylaminopyridine (cat. amount) was added to the mixture of acetic anhydride (0.162 mL), diisopropylethylamine (0.697 mL) and the product from step (ii) (760 mg) in THF (10 mL). After the mixture was stirred at RT for 3.5 h, the reaction mixture was diluted with water and sat. sodium hydrogen dicarbonate and extracted with EtOAc. The combined organic layer was washed with water and brine, dried and concentrated under reduced pressure to afford the crude product as pale yellow oil, which was used for next reaction without further purification; 1H NMR (CDCl3); 6.81 (1H, d), 6.44 (1H, d), 6.38 (1H, dd), 4.79 (2H, br s), 4.25-4.15 (1H, m), 3.99 (2H, t), 3.96-3.88 (2H, m), 3.85 (3H, s), 3.76 (2H, t), 3.58 (2H, s), 2.33 (3H, s), 1.97 (3H, s), 2.00-1.88 (2H, m), 1.86-1.71 (1H, m), 1.64-1.50 (1H, m), 1.48-1.32 (1H, m), 1.30-0.95 (3H, m), 0.86 (9H, s), 0.76 (3H, t), 0.02 (6H, s); LC-MS: m/z 576.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layer was washed with water and brine
  3. customdried
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e2eb4b1d6e9d42c5b3b1837f79e22359
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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