Water → 2,5-Difluoro-4-{2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenoxy}-N-1,3-thiazol-4-ylbenzenesulfonamide

HRID 46260Notes

Reaction equation

HRID 46260 reaction equation
[CH3:1][N:2]1[CH2:5][CH:4]([N:6]2[C:10]([C:11]3[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=3[OH:21])=[CH:9][CH:8]=[N:7]2)[CH2:3]1.CC(C)([O-])C.[K+].[S:28]1[CH:32]=[C:31]([N:33]([S:41]([C:44]2[CH:49]=[C:48]([F:50])[C:47](F)=[CH:46][C:45]=2[F:52])(=[O:43])=[O:42])C(=O)OC(C)(C)C)[N:30]=[CH:29]1.O>C(#N)C>[F:52][C:45]1[CH:46]=[C:47]([O:21][C:12]2[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=2[C:10]2[N:6]([CH:4]3[CH2:3][N:2]([CH3:1])[CH2:5]3)[N:7]=[CH:8][CH:9]=2)[C:48]([F:50])=[CH:49][C:44]=1[S:41]([NH:33][C:31]1[N:30]=[CH:29][S:28][CH:32]=1)(=[O:43])=[O:42]

Participants

6

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 59436528tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamateHCID 1360636172-[1-(1-Methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenol

Product 1

HCID 468416472,5-Difluoro-4-{2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenoxy}-N-1,3-thiazol-4-ylbenzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-[1-(1-Methylazetidin-3-yl)-1H-pyrazol-5-yl]-4-(trifluoromethyl)phenol, (Preparation 855, 137 mg, 0.00046 mol) was dissolved in acetonitrile (10 mL) and treated with potassium tert-butoxide (57 mg, 0.0005 mol) and stirred under nitrogen for 30 minutes. Tert-butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamate, (Preparation 297, 182 mg, 0.00046 mol) was added and the solution stirred for 2 hours. Water (0.2 mL) was added and the solution evaporated. The residue was suspended in water and extracted with ethyl acetate (1×20 mL). The organic layer was separated and washed with brine (2×20 mL). The organic layer was separated, dried over anhydrous sodium sulphate, filtered and evaporated to give a foam. The foam was purified using an ISCO™ Companion (4 g. silica gel, eluting with dichloromethane:acetic acid 99.5:0.5 to dichloromethane:methanol:acetic acid 95:5:0.5). The appropriate fractions were evaporated to give a film. The film was triturated with diethyl ether to give the title compound as a white solid (11 mg).

Workup

  1. additionwas added
  2. stirringthe solution stirred for 2 hours
  3. customthe solution evaporated
  4. extractionextracted with ethyl acetate (1×20 mL)
  5. customThe organic layer was separated
  6. washwashed with brine (2×20 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous sodium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customto give a foam
  12. customThe foam was purified
  13. washan ISCO™ Companion (4 g. silica gel, eluting with dichloromethane:acetic acid 99.5:0.5 to dichloromethane:methanol:acetic acid 95:5:0.5)
  14. customThe appropriate fractions were evaporated
  15. customto give a film
  16. customThe film was triturated with diethyl ether

Sources & evidence

ORD record
ord-4b6485e7658d49379e222e7268ba2747
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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