Dimethylformamide → N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide

HRID 1670922Notes

Reaction equation

HRID 1670922 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[C:26]([F:27])=[CH:25][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.CN(C=O)C.C1C(=O)N(Br)C(=O)C1.[CH3:43][CH:44]([CH3:48])[C:45](=[S:47])[NH2:46]>CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:47][C:45]([CH:44]([CH3:48])[CH3:43])=[N:46][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][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 6228DimethylformamideHCID 67184N-bromobutanimideHCID 109095072-Methylpropanethioamide2×HCID 57989720N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Product 1

HCID 57989924N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamideYield 45.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 250 mL flask was placed N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (4 g, 9.05 mmol) and DMF (60 mL) was added. NBS (1.62 g, 9.10 mmol) was added and, after stirring at rt for 40 min, 2-methylpropanethioamide (1.4 g, 13.6 mmol), prepared by a procedure analogous to Intermediate 1, was added. After 4 h at rt, the reaction mixture was poured into 800 mL of EtOAc and washed 4 times with 250 mL of H2O, washed once with 200 mL of brine, and dried over NaSO4. Silica gel was added and the volatiles were removed under reduced pressure. Column chromatography with 10% to 60% EtOAc:Hexane gave 2.15 g (45%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 9.06 (d, J=5.3 Hz, 1H), 8.12-8.30 (m, 1H), 7.93-8.06 (m, 2H), 7.84 (t, J=7.9 Hz, 1H), 7.75 (t, J=9.2 Hz, 2H), 7.37 (d, J=5.3 Hz, 1H), 3.77-3.93 (m, 1H), and 1.89 (d, J=6.8 Hz, 6H). MS (ESI): 524 [M]+.

Workup

  1. customIn a 250 mL flask was placed
  2. additionwas added
  3. waitAfter 4 h at rt
  4. washwashed 4 times with 250 mL of H2O
  5. washwashed once with 200 mL of brine
  6. dry with materialdried over NaSO4
  7. additionSilica gel was added
  8. customthe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-ecfbaef06193443586c1936695bca0af
Source dataset
uspto-grants-2011_08
Patent number
US07994185B2

Reaction notes

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