Methanesulfonyl chloride → N-(3-{5-(2-Chloro-4-pyrimidinyl)-2-[4-(methylsulfonyl)-1-piperazinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

HRID 1961928Notes

Reaction equation

HRID 1961928 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[N:12]=[C:11]([C:13]2[S:17][C:16]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:15][C:14]=2[C:24]2[C:25]([F:42])=[C:26]([NH:30][S:31]([C:34]3[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=3[F:41])(=[O:33])=[O:32])[CH:27]=[CH:28][CH:29]=2)[CH:10]=[CH:9][N:8]=1>C(Cl)Cl>[Cl:6][C:7]1[N:12]=[C:11]([C:13]2[S:17][C:16]([N:18]3[CH2:23][CH2:22][N:21]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:20][CH2:19]3)=[N:15][C:14]=2[C:24]2[C:25]([F:42])=[C:26]([NH:30][S:31]([C:34]3[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=3[F:41])(=[O:33])=[O:32])[CH:27]=[CH:28][CH:29]=2)[CH:10]=[CH:9][N:8]=1

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 57989746N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-piperazinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide

Product 1

HCID 57989647N-(3-{5-(2-Chloro-4-pyrimidinyl)-2-[4-(methylsulfonyl)-1-piperazinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamideYield 32.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.05 mL, 0.7 mmol) was added to a stirring solution of N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1-piperazinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (0.40 g, 0.66 mmol) and TEA (0.32 mL, 2.3 mmol) in DCM (10 mL) at rt. LCMS analysis indicated clean conversion to product. The reaction was quenched with water and the whole was extracted with DCM. The combined organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated onto silica gel. Purification by flash chromatography afforded the title compound of Step D (0.14 g, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.80 (s, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.25-7.63 (m, 5H), 6.50 (d, J=5.3 Hz, 1H), 3.69 (br. s., 4H), 3.27 (br. s., 4H), 2.93 (s, 3H).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe whole was extracted with DCM
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated onto silica gel
  6. customPurification by flash chromatography

Sources & evidence

ORD record
ord-ae932b4abcf04e79b9412bb68885f9d5
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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