Pyridine → N-[3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide

HRID 1670930Notes

Reaction equation

HRID 1670930 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:24])=[C:19]([CH:21]=[CH:22][CH:23]=2)[NH2:20])[CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=1[S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:24])=[C:19]([NH:20][S:39]([C:33]3[CH:34]=[C:35]([F:38])[CH:36]=[CH:37][C:32]=3[F:31])(=[O:41])=[O:40])[CH:21]=[CH:22][CH:23]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 27369112,5-Difluorobenzenesulfonyl chlorideHCID 579898453-(2-Tert-butyl-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluoroaniline

Product 1

HCID 44516823N-[3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamideYield 45.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluoroaniline (30 g, 82.8 mmol) in DCM (250 mL) was added pyridine (19.6 g, 248 mmol). The mixture was cooled to 0° C. 2,5-Difluorobenzene-1-sulfonyl chloride (17.6 g, 82.8 mmol) in DCM (20 mL) was added dropwise to the mixture. The reaction was stirred at rt overnight. Then the reaction was washed with water (300 mL), and extracted with DCM (2×400 mL). The organic layer was washed with brine, dried over anhydrous NaSO4, filtrated and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (petroleum ether:EtOAc:DCM 20:1:5) to afford the title compound (20.4 g, 45.8% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.26 (d, J=5.3 Hz, 1H), 7.60-7.66 (m, 1H), 7.51-7.60 (m, 1H), 7.30-7.36 (m, 1H), 7.17-7.30 (m, 3H), 7.07-7.17 (m, 1H), 6.68 (d, J=5.3 Hz, 1H), 1.45 (s, 9H). MS (ES+): 539 [M+H]+.

Workup

  1. washThen the reaction was washed with water (300 mL)
  2. extractionextracted with DCM (2×400 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous NaSO4
  5. filtrationfiltrated
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product, which
  8. customwas purified by column chromatography on silica gel (petroleum ether:EtOAc:DCM 20:1:5)

Sources & evidence

ORD record
ord-969721203d494509831d3eba16fdc6ca
Source dataset
uspto-grants-2011_08
Patent number
US07994185B2

Reaction notes

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