Acetyl chloride → HCID 118483526, compound

HRID 58492Notes

Reaction equation

HRID 58492 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:25]4[CH2:24][CH2:23][NH:22][CH2:21][C:20]=4[NH:19][N:18]=3)=[O:16])[CH2:11][CH2:10]2)=[C:5]([C:26]([F:29])([F:28])[F:27])[CH:4]=1.C(N(C(C)C)CC)(C)C.[C:39](Cl)(=[O:41])[CH3:40]>CN(C=O)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:25]4[CH2:24][CH2:23][N:22]([C:39](=[O:41])[CH3:40])[CH2:21][C:20]=4[NH:19][N:18]=3)=[O:16])[CH2:11][CH2:10]2)=[C:5]([C:26]([F:29])([F:27])[F:28])[CH:4]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 118483549HCID 118483549, compound

Product 1

HCID 118483526HCID 118483526, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-3-yl)methanone hydrochloride (63 mg, 0.15 mmol) and diisopropylethylamine (70 L, 0.40 mmol) in DMF (3.0 mL) was added acetyl chloride (11 μL, 0.15 mmol). The mixture was stirred for 16 hour. The solvent was removed under reduced pressure and the residue was diluted with H2O (10 mL) and extracted with EtOAc (2×10 mL). The combined organic extracts were washed with saturated brine (1×20 mL), dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 100% (10% CH3OH in CH2Cl2 with 0.01% NH4OH) in CH2Cl2) and further purified by reverse phase chromatography (Isco CombiFlash Rf unit, 12 g Redisep c18 gold column, 0% to 100% acetonitrile in water) to give 1-(3-(4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidine-1-carbonyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)ethanone as a white solid (20 mg, 94%): mp 176-180° C.; 1H NMR (500 MHz, DMSO-d6) δ 12.86 (s, 1H), 7.71-7.68 (m, 1H), 7.56-7.49 (m, 2H), 4.94-4.55 (m, 3H), 3.66-3.62 (m, 2H), 3.10 (br s, 2H), 2.85-2.48 (m, 4H), 2.10-2.08 (m, 3H), 1.73 (m, 4H); ESI MS m/z 439 [M+H]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with H2O (10 mL)
  3. extractionextracted with EtOAc (2×10 mL)
  4. washThe combined organic extracts were washed with saturated brine (1×20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe resulting residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 100% (10% CH3OH in CH2Cl2 with 0.01% NH4OH) in CH2Cl2)
  8. customfurther purified by reverse phase chromatography (Isco CombiFlash Rf unit, 12 g Redisep c18 gold column, 0% to 100% acetonitrile in water)

Sources & evidence

ORD record
ord-21e8d1c9a3fc48d28b54bf4637ae0710
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

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