Acetyl chloride → HCID 57978667, compound

HRID 1866863Notes

Reaction equation

HRID 1866863 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

5

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 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)+.

Workup

  1. extractionextracted three times with methylene chloride
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. additionThe crude intermediary acylhydrazide was treated with thionyl chloride (˜1 mL, excess)
  6. waitthe resulting mixture was aged for approximately 18 h
  7. additionThe reaction mixture was poured carefully into cold saturated aqueous sodium bicarbonate
  8. extractionextracted three times with methylene chloride
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe 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)

Sources & evidence

ORD record
ord-57134fadd0a04e0dbf58996773de4e8c
Source dataset
uspto-grants-2009_12
Patent number
US07629467B2

Reaction notes

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