Acetyl chloride → HCID 57905216, compound

HRID 1093151Notes

Reaction equation

HRID 1093151 reaction equation
[CH2:1]1[CH:6]2[CH2:7][N:8]3[C:13](=[O:14])[C:12]([OH:15])=[C:11]([C:16]([NH:18][CH2:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[O:17])[N:10]=[C:9]3[C:3]([NH2:27])([CH2:4][O:5]2)[CH2:2]1.CCN(CC)CC.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl>[CH3:36][C:35]([NH:27][C:3]12[CH2:4][O:5][CH:6]([CH2:7][N:8]3[C:13](=[O:14])[C:12]([OH:15])=[C:11]([C:16]([NH:18][CH2:19][C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[O:17])[N:10]=[C:9]31)[CH2:1][CH2:2]2)=[O:37]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 57904795HCID 57904795, compound

Product 1

HCID 57905216HCID 57905216, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 10-amino-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-(epoxymethano)pyrimido[1,2-a]azepine-2-carboxamide (30 mg, 0.080 mmol) in CH2Cl2 (2 mL) was added Et3N (0.056 mL, 0.401 mmol) followed by acetyl chloride (0.05 mL, 0.401 mmol) and the resulting mixture stirred at room temperature for 16 h. The reaction mixture was concentrated and the resulting residue dissolved in methanol (2 mL) and treated with 2M dimethylamine in methanol (0.5 mL). The resulting reaction mixture was stirred at 60° C. for 2 h, cooled and purified by preparative HPLC to afford the title compound as a white solid (9 mg, 27% yield). 1H NMR (500 MHz, CDCl3) δ: 11.92 (s, 1H), 7.39 (brs, 1H), 7.29-7.33 (m, 2H), 7.05-7.09 (m, 2H), 6.13 (s, 1H), 4.59-4.65 (m, 2H), 4.48-4.55 (m, 3H), 4.30 (d, 1H, J=11.9 Hz), 4.10 (d, 1H, J=16.17 Hz), 2.52-2.58 (m, 1H), 2.30-2.36 (m, 1H), 1.82 (s, 3H), 1.75-1.82 (m, 1H), 1.50-1.55 (m, 1H). LCMS (M+H)=417.25. HPLC purity>95%.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe resulting residue dissolved in methanol (2 mL)
  3. additiontreated with 2M dimethylamine in methanol (0.5 mL)
  4. customThe resulting reaction mixture
  5. stirringwas stirred at 60° C. for 2 h
  6. temperaturecooled
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-87af11c78ac44109a2b87efc2fab3926
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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