Acetyl chloride → HCID 57978667, compound

Reaction equation

[C:1](Cl)(=[O:3])[CH3:2].[C:5]1([C:11]2([C:18]3[CH:27]=[C:26]([O:28][CH2:29][C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH:25]=[CH:24][C:19]=3[C:20]([NH:22][NH2:23])=O)[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>>[CH3:2][C:1]1[O:3][C:20]([C:19]2[CH:24]=[CH:25][C:26]([O:28][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:27][C:18]=2[C:11]2([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)=[N:22][N:23]=1

Participants

Reactant 4

HCID 6367Acetyl chloride

HCID 8471Triethylamine

HCID 516892Sodium Bicarbonate

HCID 57978651HCID 57978651, compound

Product 1

HCID 57978667HCID 57978667, compound

Procedure

Acetyl chloride (10.0 μL, 0.14 mmol) was added to a stirred solution of 4d (50.0 mg, 0.11 mmol) and triethylamine (38.0 μL, 0.27 mmol) in THB (900 μL) at room temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with methylene chloride. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude intermediary acylhydrazide was treated with thionyl chloride (˜1 mL, excess), and the resulting mixture was aged for approximately 18 h. The reaction mixture was poured carefully into cold saturated aqueous sodium bicarbonate and extracted three times with methylene chloride. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (gradient elution; 20-100% acetonitrile/water as eluent, 0.1% TFA as modifier). Lyophilization of the purified fractions afforded the title compound 5d, m/z (ES) 488 (MH)+.