Acetyl chloride → HCID 178503210, compound

HRID 724316Notes

Reaction equation

HRID 724316 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:27])[C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[N:13][C:12]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:35](Cl)(=[O:37])[CH3:36]>ClCCl>[C:35]([NH:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:27])[C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[N:13][C:12]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)[CH2:5][CH2:4]1)(=[O:37])[CH3:36]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 178503208HCID 178503208, compound

Product 1

HCID 178503210HCID 178503210, compoundYield 32.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(cis-4-Amino-cyclohexyl)-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide hydrochloride (150 mg, 0.364 mmol) was suspended in dichloromethane (2 ml) under nitrogen at room temperature and triethylamine (153 μl, 1.09 mmol) was added followed by acetyl chloride (29 μl, 0.4 mmol). The reaction was stirred at room temperature for 1.5 h and the mixture was quenched with sat. sodium bicarbonate solution (3 ml). The organic phase was separated and the aqueous phase was washed with dichloromethane (2×5 ml). The combined organic extracts were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:concentrated aqueous ammonia (95:5:0.5, by volume) and the product was triturated with diethylether (2×3 ml) to give N-(cis-4-Acetylamino-cyclohexyl)-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide (50 mg) as a white solid.

Workup

  1. customthe mixture was quenched with sat. sodium bicarbonate solution (3 ml)
  2. customThe organic phase was separated
  3. washthe aqueous phase was washed with dichloromethane (2×5 ml)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane
  7. custommethanol:concentrated aqueous ammonia (95:5:0.5, by volume) and the product was triturated with diethylether (2×3 ml)

Sources & evidence

ORD record
ord-828806f9ab06478c96b9a0543941c8bf
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

Loading…