Pyridine-3-sulfonyl chloride → N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-pyridinesulfonamide

HRID 239383Notes

Reaction equation

HRID 239383 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:26])=[C:21]([CH:23]=[CH:24][CH:25]=2)[NH2:22])[CH:5]=[CH:4][N:3]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([S:33](Cl)(=[O:35])=[O:34])[CH:28]=1>N1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[N:10][C:9]=2[C:19]2[C:20]([F:26])=[C:21]([NH:22][S:33]([C:29]3[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=3)(=[O:35])=[O:34])[CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 3164136Pyridine-3-sulfonyl chlorideHCID 579897213-(5-(2-Chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-fluoroaniline

Product 1

HCID 57989773N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-pyridinesulfonamideYield 71.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 3-(5-(2-chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-fluoroaniline (3 g, 7.7 mmol) in pyridine (15 mL) was added pyridine-3-sulfonyl chloride (1.49 g, 8.4 mmol) dropwise to the mixture. The reaction was stirred at rt overnight. The reaction was washed with water (100 mL), and extracted with DCM (2×100 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (petroleum ether:EtOAc 5:1) to afford the title compound of Step A (2.9 g, 71.5% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.55-10.60 (br, 1H), 8.82-8.86 (m, 1H), 8.72-8.76 (m, 1H), 8.30 (d, J=5.3 Hz, 1H), 8.07-8.13 (m, 1H), 7.51-7.52 (m, 1H), 7.39-7.47 (m, 1H), 7.27-7.40 (m, 2H), 6.47 (d, J=5.3 Hz, 1H) 3.47-3.57 (m, 4H), 3.67-3.75 (m, 4H). MS (ES+): 533 [M+H]+.

Workup

  1. washThe reaction was washed with water (100 mL)
  2. extractionextracted with DCM (2×100 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product, which
  8. customwas purified by column chromatography on silica gel (petroleum ether:EtOAc 5:1)

Sources & evidence

ORD record
ord-1e7987c473a64e0a823bb80bbbee9092
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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