Acetyl chloride → HCID 66588889, compound

HRID 1093147Notes

Reaction equation

HRID 1093147 reaction equation
Cl.C([N:9]([C@@H:13]1[C@@:20]2([CH3:24])[C:21]([CH3:23])([CH3:22])[C@H:17]([CH2:18][CH2:19]2)[CH2:16][N:15]2[C:25](=[O:41])[C:26]([OH:40])=[C:27]([C:29](=[O:39])[NH:30][CH2:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[N:28]=[C:14]12)[C:10](=O)[OH:11])C1C=CC=CC=1.[CH:42](N(C(C)C)CC)(C)C.C(Cl)(=O)C.N(C)C.CO>C(Cl)Cl>[C:10]([NH:9][C@@H:13]1[C@@:20]2([CH3:24])[C:21]([CH3:22])([CH3:23])[C@H:17]([CH2:18][CH2:19]2)[CH2:16][N:15]2[C:25](=[O:41])[C:26]([OH:40])=[C:27]([C:29]([NH:30][CH2:31][C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)=[O:39])[N:28]=[C:14]12)(=[O:11])[CH3:42]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 22497844Dimethylamine methanolHCID 66588908HCID 66588908, compound

Product 1

HCID 66588889HCID 66588889, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of benzyl((7S,10R,11R)-2-((4-fluorobenzyl)carbamoyl)-3-hydroxy-10,12,12-trimethyl-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,10-methanopyrimido[1,2-a]azocin-11-yl)carbamate hydrochloride salt (0.025 g, 0.055 mmol) and diisopropyl-ethylamine (0.175 mL, 1 mmol) in CH2Cl2 (3 mL) was added acetyl chloride (0.036 mL, 0.5 mmol). After 4 h, 2M Me2NH/methanol (1 mL) was added and stirring continued at room temperature. After 16 h, the reaction mixture was concentrated and purified by preparative-HPLC using methanol/water (0.1% trifluoroacetic acid) to afford the title compound (0.0188 g, 0.038 mmol, 69% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ: 11.99 (1H, s), 7.56 (1 H, t, J=5.8 Hz), 7.33 (2 H, dd, J=8.5, 5.2 Hz), 7.04-7.09 (2 H, m), 6.42 (1 H, d, J=9.2 Hz), 5.52 (1 H, d, J=9.2 Hz), 5.17 (1 H, dd, J=15.4, 8.7 Hz), 4.54-4.66 (2 H, m, J=14.8, 14.6, 14.6, 6.0 Hz), 3.70 (1 H, d, J=15.3 Hz), 3.48 (3H, s, from CH3OH), 2.09 (1 H, t, J=8.1 Hz), 1.94 (3 H, s), 1.78-1.87 (1 H, m), 1.41-1.49 (1 H, m), 1.38 (3 H, s), 1.30-1.37 (1 H, m), 0.99 (3 H, s), 0.95-0.98 (1 H, m), 0.94 (3 H, s). LCMS (M+H) calcd for C24H30FN4O4: 457.23; found: 457.27. Purity: >98%.

Workup

  1. customcontinued at room temperature
  2. waitAfter 16 h
  3. concentrationthe reaction mixture was concentrated
  4. custompurified

Sources & evidence

ORD record
ord-7179c8128fb6447e83d0aea1da2d325d
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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