Potassium Carbonate → tert-butyl {[4-(4-chloro-2-{1-[1-(diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}phenoxy)-3-cyanophenyl]sulfonyl}1,3-thiazol-4-ylcarbamate

HRID 1402020Notes

Reaction equation

HRID 1402020 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[N:13]([CH:14]3[CH2:17][N:16]([CH:18]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:15]3)[N:12]=[CH:11][CH:10]=2)[CH:3]=1.[C:31]([C:33]1[CH:34]=[C:35]([S:40]([N:43]([C:51]2[N:52]=[CH:53][S:54][CH:55]=2)[C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:42])=[O:41])[CH:36]=[CH:37][C:38]=1F)#[N:32].C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:38]2[CH:37]=[CH:36][C:35]([S:40]([N:43]([C:51]3[N:52]=[CH:53][S:54][CH:55]=3)[C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:42])=[O:41])=[CH:34][C:33]=2[C:31]#[N:32])=[C:4]([C:9]2[N:13]([CH:14]3[CH2:17][N:16]([CH:18]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:15]3)[N:12]=[CH:11][CH:10]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 59436569tert-Butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamateHCID 1360636302-[2-(1-Benzhydryl-azetidin-3-yl)-2H-pyrazol-3-yl]-4-chloro-phenol

Product 1

HCID 59436484tert-butyl {[4-(4-chloro-2-{1-[1-(diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}phenoxy)-3-cyanophenyl]sulfonyl}1,3-thiazol-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

4-chloro-2-{1-[1-(diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}phenol, (Preparation 689, 75 mg, 0.18 mmol), tert-butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 250, 69 mg, 0.18 mmol), potassium carbonate (62 mg, 0.45 mmol) and dimethyl sulphoxide (4 ml) were combined and stirred at room temperature under nitrogen for 4 hours. Saturated aqueous ammonium chloride solution (20 ml) was added and the mixture extracted with ethyl acetate (1×20 ml). The organic layer was separated and back-washed with saturated aqueous sodium chloride solution (2×20 ml). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give an oil. The oil was purified using an ISCO® Companion (4 g. silica gel, gradient from dichloromethane to dichloromethane:methanol 98:2). The appropriate fractions were combined and solvents removed in vacuo to give the title compound as a glass. Yield 33 mg. 24%.

Workup

  1. extractionthe mixture extracted with ethyl acetate (1×20 ml)
  2. customThe organic layer was separated
  3. washback-washed with saturated aqueous sodium chloride solution (2×20 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customto give an oil
  9. customThe oil was purified
  10. customsolvents removed in vacuo

Sources & evidence

ORD record
ord-27f8dd45712b413797da4a85c2e80698
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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