Water → N-{5-[5-(2-Chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide

HRID 239276Notes

Reaction equation

HRID 239276 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[CH:13][C:14]([F:29])=[C:15]([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:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[O:38]1[CH2:43][CH2:42][CH:41]([C:44](=[S:46])[NH2:45])[CH2:40][CH2:39]1.O>CC(N(C)C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:46][C:44]([CH:41]3[CH2:42][CH2:43][O:38][CH2:39][CH2:40]3)=[N:45][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([F:29])=[C:15]([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:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 13197204Oxane-4-carbothioamideHCID 86636577N-{5-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide

Product 1

HCID 57989666N-{5-[5-(2-Chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamideYield 58.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{5-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (0.910 g, 2.06 mmol) (prepared in a manner analogous to Intermediate 35) in DMA (8.24 mL) was added NBS (0.385 g, 2.16 mmol). The reaction stirred 30 min at rt and then tetrahydro-2H-pyran-4-carbothioamide (0.389 g, 2.68 mmol) was added. The reaction stirred 16 h at rt. The reaction mixture was poured into water (150 mL), causing precipitation of a solid. The solid was collected by vacuum filtration, redissolved in EtOAc (50 mL), and concentrated onto silica gel. Purification by chromatography (20 to 100% EtOAc:hexanes) afforded the title compound (690 mg, 1.21 mmol, 58.5% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.86 (s, 1H), 8.58 (d, J=5.3 Hz, 1H), 7.45-7.69 (m, 4H), 7.42 (dd, J=7.5, 2.0 Hz, 1H), 7.32 (dd, J=10.1, 8.8 Hz, 1H), 7.14 (d, J=5.3 Hz, 1H), 3.95 (dd, J=11.7, 2.0 Hz, 2H), 3.40-3.56 (m, 2H), 3.25-3.41 (m, 1H), 2.02 (dd, J=12.9, 1.6 Hz, 2H), 1.65-1.86 (m, 2H). MS (ESI): 567.09 [M+H]+.

Workup

  1. stirringThe reaction stirred 16 h at rt
  2. customprecipitation of a solid
  3. filtrationThe solid was collected by vacuum filtration
  4. dissolutionredissolved in EtOAc (50 mL)
  5. concentrationconcentrated onto silica gel
  6. customPurification by chromatography (20 to 100% EtOAc:hexanes)

Sources & evidence

ORD record
ord-b06160c6e69645f3ba9ca3e9fd58821c
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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