Acetyl chloride → HCID 178474012, compound

HRID 874459Notes

Reaction equation

HRID 874459 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[N:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.C(N(CC)CC)C.[C:35](Cl)(=[O:37])[CH3:36]>ClCCl>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:19]2[C:10]3=[C:11]4[C:15](=[C:6]5[N:5]([CH3:27])[CH:4]=[CH:3][C:2]([NH:1][C:35](=[O:37])[CH3:36])=[C:7]5[CH:8]=[N:9]3)[C:14](=[O:16])[NH:13][C:12]4=[CH:17][CH2:18]2)=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 6367Acetyl chloride2×HCID 8471Triethylamine2×HCID 178480437HCID 178480437, compound

Product 1

HCID 178474012HCID 178474012, compoundYield 80.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of Example 69e (0.02 g, 0.053 mmol), triethylamine (53.6 mg, 0.53 mmol), and acetyl chloride (0.019 mL, 0.265 mmol) in dichloromethane (2 mL) was stirred at ambient temperature for 2 hours. Additional acetyl chloride (0.057 mL, 0.795 mmol) and triethylamine (161 mg, 1.59 mmol) were added, and the reaction mixture was stirred for additional 3 hours. The solvent was evaporated, and the residue was treated with dioxane (3 mL) and 2.0 NaOH (1 mL). The reaction mixture was heated at 80° C. for three hours. The solvents were partially removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was neutralized with 10% HCl and extracted with additional ethyl acetate twice. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase HPLC(C18, CH3CN/water (0.1% TFA), 0-100%) to afford 0.018 g (67.3%) of the title compound as the TFA salt. 1H NMR (500 MHz, DMSO-d6) δ 10.87 (d, J=5.8, 1H), 10.31 (s, 1H), 8.53 (d, J=2.75 Hz, 1H), 8.42 (d, J=2.44 Hz, 1H), 7.74 (s, 1H), 7.09 (d, J=5.49 Hz, 1H), 7.03-7.07 (m, 2H), 6.57-6.60 (m, 2H), 4.65 (br s, 2H), 4.07 (s, 3H), 2.13 (s, 3H). MS (DCI+) m/z 420.2 (M+H)+.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue was treated with dioxane (3 mL) and 2.0 NaOH (1 mL)
  3. customThe solvents were partially removed
  4. customthe residue was partitioned between water and ethyl acetate
  5. extractionextracted with additional ethyl acetate twice
  6. washThe combined organic layers were washed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by reverse phase HPLC(C18, CH3CN/water (0.1% TFA), 0-100%)

Sources & evidence

ORD record
ord-566b4e0a7795469e9f867df241ceef62
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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