Acetic Acid → HCID 118566709, compound

HRID 1056805Notes

Reaction equation

HRID 1056805 reaction equation
[F:1][C:2]1([F:29])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([C:23]4[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=4)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1.[CH3:30][C:31]([CH3:33])=O.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl>[F:29][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([C:23]4[CH2:24][CH2:25][N:26]([CH:31]([CH3:33])[CH3:30])[CH2:27][CH:28]=4)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5003444Sodium cyanoborohydrideHCID 131736448HCID 131736448, compound

Product 1

HCID 118566709HCID 118566709, compoundYield 63.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of 6-chloro-2-(1,2,3,6-tetrahydro-pyridin-4-yl)-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide (150.00 mg, 0.33 mmol, 1.00 eq) in 1,2-dichloroethane (5.00 mL, 33.33 V) was added acetone (0.05 mL, 0.66 mmol, 2.00 eq) and glacial acetic acid (0.04 mL, 0.66 mmol, 2.00 eq), then the reaction mixture was stirred at RT for 1 h and then cooled to 0° C. Sodium cyanoborohydride (43.54 mg, 0.66 mmol, 2.00 eq) was added and stirred at RT for 16 h. The solvent was removed and the crude product was purified by flash column chromatography using to afford 6-chloro-2-(1-isopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexyl methyl)-amide (100.00 mg, 0.21 mmol, 62.5%, pale yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.83 (t, J=6.03 Hz, 1H), 8.00-7.96 (m, 3H), 7.76 (d, J=9.02 Hz, 1H), 6.91 (s, 1H), 3.27 (t, J=6.12 Hz, 4H), 2.70-2.65 (m, 4H), 2.04-2.02 (m, 2H), 1.86-1.74 (m, 5H), 1.33-1.17 (m, 2H), 1.05 (br s, 6H). m/z: 462.3 [M+H]+

Workup

  1. temperaturecooled to 0° C
  2. stirringstirred at RT for 16 h
  3. customThe solvent was removed
  4. customthe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-346ace1b1acc4b45b6f1a7af4e08d148
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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