2,6-Difluorobenzenesulfonyl chloride → 1,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate

HRID 1962087Notes

Reaction equation

HRID 1962087 reaction equation
[NH2:1][C:2]1[C:3]([F:33])=[C:4]([C:8]2[N:9]=[C:10]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]3)[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[N:14]=2)[CH:5]=[CH:6][CH:7]=1.[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=1[S:42](Cl)(=[O:44])=[O:43]>N1C=CC=CC=1>[Cl:19][C:15]1[N:14]=[C:13]([C:12]2[S:11][C:10]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:22][CH2:21]3)=[N:9][C:8]=2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][S:42]([C:36]3[C:37]([F:41])=[CH:38][CH:39]=[CH:40][C:35]=3[F:34])(=[O:44])=[O:43])[C:3]=2[F:33])[CH:18]=[CH:17][N:16]=1

Participants

4

Reactant 2

HCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 579900771,1-Dimethylethyl 4-[4-(3-amino-2-fluorophenyl)-5-(2-chloro-4-pyrimidinyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate

Product 1

HCID 579899421,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylateYield 79.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-[4-(3-amino-2-fluorophenyl)-5-(2-chloro-4-pyrimidinyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate (300 mg, 0.612 mmol) in pyridine (3 mL) was added 2,6-difluorobenzenesulfonyl chloride (130 mg, 0.612 mmol), and the reaction mixture was stirred for 3 h. The reaction mixture was quenched with water (5 mL) and extracted with EtOAc (3×). The extracts were dried, filtered and concentrated. The residue was purified using column chromatography (40 to 100% EtOAc/hexane) to give 324 mg of the title compound. MS (ESI): 610.1 [M+1-56]+.

Workup

  1. customThe reaction mixture was quenched with water (5 mL)
  2. extractionextracted with EtOAc (3×)
  3. customThe extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified

Sources & evidence

ORD record
ord-953342f52b854e6aac5e6df7272b019c
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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