Dimethylformamide → 5-Chloro-2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

HRID 222801Notes

Reaction equation

HRID 222801 reaction equation
[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[CH:20][C:19](=[O:23])[N:18]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:17]=2[CH3:30])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1.[Cl:31]N1C(=O)CCC1=O.CN(C)C=O>>[CH:1]1([C@H:5]([NH:13][C:14]([C:16]2[C:21]([CH3:22])=[C:20]([Cl:31])[C:19](=[O:23])[N:18]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:17]=2[CH3:30])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 31398ChlorosuccinimideHCID 583075042,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

Product 1

HCID 532390065-Chloro-2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amideYield 67.1%

Procedure

A mixture of 2,4-dimethyl-6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide (13.9 mg, 0.0343 mmol) and N-chlorosuccinimide (5.33 mg, 0.0399 mmol) in N,N-dimethylformamide (0.3 mL, 4 mmol) was stirred at r.t. for 30 min. It was quenched and stirred with water (4 ml) for 5 min, then filtered, washed with water and dried in vacuo to give 10.1 mg of the title compound as a colourless solid, yield 67%. LC-MS (m/z) 439.4 & 441.6 (3:1, MH+); tR=1.52 (method C). 1H NMR (T=+70° C., 500 MHz, DMSO-d6, DMSO-d5=2.50 ppm): 1.77 (overlapping s, 3H, Me), 1.70-1.92 (overlapping m, 5H), 2.07 (br. m, 1H), 2.17 (s, 3H, Me), 2.67 (m, 1H, CH of Cb), 4.94 (t, J=8.3 Hz, CH—N), 7.03 (br. t, 1H), 7.14 (br. d, J=9.8 Hz, 1H), 7.18 (br. d, J=7.7 Hz, 1H), 7.22 (br., 2H, Ph), 7.35 (br. m, 1H), 7.5 (br. t, 1H, para-H of Ph), 7.55 (br. m, 2H, two meta-H of Ph), 8.68 (br. d, 1H, NH).

Workup

  1. customIt was quenched
  2. stirringstirred with water (4 ml) for 5 min
  3. filtrationfiltered
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-6aa87e7dd4d74650b8a33e7992a2880f
Source dataset
uspto-grants-2012_06
Patent number
US08207347B2

Reaction notes

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