Potassium Carbonate → Tert-butyl 4-{4-[4-(2-chloro-4-{[(2,4-dimethoxybenzyl)(pyrimidin-2-yl)amino]sulfonyl}-5-fluorophenoxy)-4'-(trifluoromethyl)biphenyl-3-yl]pyridin-2-yl}piperazine-1-carboxylate

HRID 1619723Notes

Reaction equation

HRID 1619723 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([N:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:19]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:43][C:44]1[C:45](F)=[CH:46][C:47]([F:71])=[C:48]([S:50]([N:53]([CH2:60][C:61]2[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][C:62]=2[O:69][CH3:70])[C:54]2[N:59]=[CH:58][CH:57]=[CH:56][N:55]=2)(=[O:52])=[O:51])[CH:49]=1>CS(C)=O>[Cl:43][C:44]1[CH:49]=[C:48]([S:50]([N:53]([CH2:60][C:61]2[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][C:62]=2[O:69][CH3:70])[C:54]2[N:55]=[CH:56][CH:57]=[CH:58][N:59]=2)(=[O:51])=[O:52])[C:47]([F:71])=[CH:46][C:45]=1[O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:16])([F:17])[F:15])=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([N:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:19]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 580422645-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamideHCID 136200880Tert-butyl 4-(4-(4-hydroxy-4'-(trifluoromethyl)biphenyl-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 58042255Tert-butyl 4-{4-[4-(2-chloro-4-{[(2,4-dimethoxybenzyl)(pyrimidin-2-yl)amino]sulfonyl}-5-fluorophenoxy)-4'-(trifluoromethyl)biphenyl-3-yl]pyridin-2-yl}piperazine-1-carboxylateYield 84.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

tert-Butyl 4-(4-(4-hydroxy-4′-(trifluoromethyl)biphenyl-3-yl)pyridin-2-yl)piperazine-1-carboxylate (Preparation 114, 240 mg, 0.480 mmol) was dissolved in dimethyl sulfoxide (3 mL) and then potassium carbonate (133 mg, 0.962 mmol) followed by 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide (Preparation 13, 219 mg, 0.480 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. The reaction was then partitioned between ethyl acetate (15 mL) and 2M HCl (5 mL). The organic layer was separated and dried over anhydrous MgSO4, filtered and evaporated. The residue was purified by flash chromatography on silica gel (gradient: 5-60% ethyl acetate in heptane) to give the title compound (380 mg, 84%) as a yellow foam.

Workup

  1. additionwere added
  2. customThe reaction was then partitioned between ethyl acetate (15 mL) and 2M HCl (5 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica gel (gradient: 5-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9534340a01f141e29b838da2772c5a89
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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