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

HRID 222800Notes

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.[Br: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]([Br: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

Conditions

Temperature: 40 °C

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 (11.8 mg, 0.0292 mmol) and N-bromosuccinimide (5.7 mg, 0.032 mmol) in N,N-dimethylformamide (0.2 mL) was shaken at 40° C. for 30 min. It was quenched and shaken with diluted aq. HCl (ca 0.1 M, 4 ml) then filtered to give the title compound as colourless solid (9.0 mg, 64% yield). LC-MS (m/z) 483.2 & 485.3 (MH+); tR=1.54. 1H NMR (T=+70° C., 500 MHz, DMSO-d6, DMSO-d5=2.50 ppm): 1.75 (overlapping s, 3H, Me), 1.72-1.93 (overlapping m, 5H), 2.07 (br. m, 1H), 2.2 (s, 3H, Me), 2.67 (m, 1H, CH of Cb), 4.93 (t, J=9.2 Hz, CH—N), 7.02 (dt, J(t)=8.3 Hz, J(d)=1.9 Hz, 1H), 7.13 (br. d, J=10.1 Hz, 1H), 7.17 (d, J=7.5 Hz, 1H), 7.22 (br. m, 2H, Ph), 7.35 (q (unres. Dt), J(t)=7.6 Hz, J(d)=6.6 Hz, 1H), 7.49 (t, J=7.3 Hz, 1H, para-H of Ph), 7.55 (t, J=6.8 Hz, 2H, two meta-H of Ph), 8.68 (d, J=8.3 Hz, 1H, NH).

Workup

customIt was quenched
stirringshaken with diluted aq. HCl (ca 0.1 M, 4 ml)
filtrationthen filtered

Sources & evidence

ORD record: ord-2c81948aeff6457cb3f388e2a3a71d91
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207347B2

Reaction notes

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