Acetyl chloride → HCID 57786724, compound

HRID 1969114Notes

Reaction equation

HRID 1969114 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([CH:28]=[CH:29][N:30]=2)[CH:5]=[C:6]([C:8]2[C:9]([CH3:27])=[C:10]([NH:14][C:15](=[O:26])[C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=3)[CH:11]=[CH:12][CH:13]=2)[CH:7]=1.C(N(C(C)C)CC)(C)C.[C:40](Cl)(=[O:42])[CH3:41]>ClCCl>[C:40]([NH:1][C:2]1[C:3]2[N:4]([CH:28]=[CH:29][N:30]=2)[CH:5]=[C:6]([C:8]2[C:9]([CH3:27])=[C:10]([NH:14][C:15](=[O:26])[C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:23])[CH3:24])=[CH:18][CH:17]=3)[CH:11]=[CH:12][CH:13]=2)[CH:7]=1)(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 42643655HCID 42643655, compound

Product 1

HCID 57786724HCID 57786724, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To N-[3-(8-Amino-imidazo[1,2-a]pyridin-6-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide (185 mg, 0.414 mmol) in dichloromethane (10 mL) was added diisopropylethylamine (0.24 mL, 3 eq). The resulting mixture was cooled to 0° C. and with stirring was added acetyl chloride (31 μL, 0.95 eq) and the resulting mixture was stirred from 0° C. to room temperature overnight. The next day the solvent was removed under reduced pressure at 55° C. and ethyl acetate (35 mL) and water (25 mL) were added to the residue. The organic layer was concentrated. Then added THF (5 mL) and 1N NaOH (5 mL) and stirred vigorously at room temperature overnight to hydrolize significant bis-amide. The next day added ethyl acetate (150 mL) and water (50 mL) and added 1N HCl to pH=2 and stirred vigorously for 10 minutes. The layers were separated, and the organic layer was washed with brine (1×50 mL), and then dried over magnesium sulfated, filtered and concentrated. The crude product was purified by Thin Layer Chromatography, eluting with 5% methanol in dichloromethane to give the title compound as an off-white powder (31 mg), ((M+H)+=441).

Workup

  1. stirringthe resulting mixture was stirred from 0° C. to room temperature overnight
  2. customThe next day the solvent was removed under reduced pressure at 55° C.
  3. additionethyl acetate (35 mL) and water (25 mL) were added to the residue
  4. concentrationThe organic layer was concentrated
  5. stirringThen added THF (5 mL) and 1N NaOH (5 mL) and stirred vigorously at room temperature overnight
  6. additionThe next day added ethyl acetate (150 mL) and water (50 mL)
  7. additionadded 1N HCl to pH=2
  8. stirringstirred vigorously for 10 minutes
  9. customThe layers were separated
  10. washthe organic layer was washed with brine (1×50 mL)
  11. dry with materialdried over magnesium
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by Thin Layer Chromatography
  15. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-e3642a82664b432cafc1c71756bf3ed4
Source dataset
uspto-grants-2013_04
Patent number
US08426441B2

Reaction notes

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