Water → 1,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperazinecarboxylate

HRID 590206Notes

Reaction equation

HRID 590206 reaction equation
C1C(=O)N(Br)C(=O)C1.[Cl:9][C:10]1[N:15]=[C:14]([CH2:16][C:17]([C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)=O)[CH:13]=[CH:12][N:11]=1.[NH2:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1)=[S:40].O>CC(N(C)C)=O>[Cl:9][C:10]1[N:15]=[C:14]([C:16]2[S:40][C:39]([N:41]3[CH2:42][CH2:43][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:45][CH2:46]3)=[N:38][C:17]=2[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[C:20]=2[F:37])[CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 12093220tert-Butyl 4-carbamothioylpiperazine-1-carboxylateHCID 86636576N-(3-(2-(2-Chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

Product 1

HCID 579899561,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperazinecarboxylateYield 47.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

NBS (0.21 g, 1.2 mmol) was added to a stirring solution of N-(3-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,5-difluorobenzenesulfonamide (0.50 g, 1.13 mmol) in DMA (5.5 ml) at rt. The reaction was allowed to stir for 15 min, then 1,1-dimethylethyl 4-(aminocarbonothioyl)-1-piperazinecarboxylate (0.55 g, 2.26 mmol) was added and the reaction was allowed to stir for 1 h. LCMS analysis indicated the reaction had progressed sufficiently, the reaction was poured into water and the bright yellow precipitate was collected by filtration. The filter cake was dissolved in DCM, dried over MgSO4, filtered and the filtrate was concentrated onto silica gel. Purification by flash chromatography afforded the title compound of Step B (0.36 g, 45% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.79 (s, 1H), 8.32 (d, J=5.5 Hz, 1H), 7.25-7.64 (m, 6H), 6.47 (d, J=5.5 Hz, 1H), 3.53-3.58 (m, 4H), 3.43-3.51 (m, 4H), 1.42 (s, 9H).

Workup

  1. stirringto stir for 1 h
  2. filtrationthe bright yellow precipitate was collected by filtration
  3. dissolutionThe filter cake was dissolved in DCM
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated onto silica gel
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-5076e61ef3394d67824fe67c173ee568
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

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