Dimethylacetamide → N-(3-{5-(2-Chloro-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

HRID 239445Notes

Reaction equation

HRID 239445 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.CC(N(C)C)=O.C1C(=O)N(Br)C(=O)C1.[CH3:44][C@H:45]1[O:50][C@@H:49]([CH3:51])[CH2:48][N:47]([C:52](=[S:54])[NH2:53])[CH2:46]1>O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:54][C:52]([N:47]3[CH2:48][C@H:49]([CH3:51])[O:50][C@H:45]([CH3:44])[CH2:46]3)=[N:53][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 67184N-bromobutanimideHCID 30122127(2R,6S)-2,6-Dimethylmorpholine-4-carbothioamideHCID 86636576N-(3-(2-(2-Chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

Product 1

HCID 57989877N-(3-{5-(2-Chloro-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamideYield 89%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To N-(3-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,5-difluorobenzenesulfonamide (1.5 g, 3.40 mmol) was added DMA (10 mL) and NBS (0.61 g, 3427 mmol). After stirring at rt for 10 min, (2R,6S)-2,6-dimethyl-4-morpholinecarbothioamide (0.800 g, 4.59 mmol) was added and stirring continued for 2 h. Water was added and the solid was collected by filtration and dried over two days to afford the title compound of Step A (1.80 g, 89% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.80 (s, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.49-7.63 (m, 3H), 7.45 (t, J=7.6 Hz, 1H), 7.39 (t, J=6.4 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 6.46 (d, J=5.3 Hz, 1H), 3.88 (d, J=11.4 Hz, 1H), 3.66 (br. s., 1H), 2.94 (s, 2H), 2.78 (s, 2H), 1.14 (d, J=6.0 Hz, 6H). m/z (ES+): 597 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued for 2 h
  3. filtrationthe solid was collected by filtration
  4. customdried over two days

Sources & evidence

ORD record
ord-3b3a5160344348f8aadcbebc3695943b
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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