Dimethyl Sulfoxide → HCID 66905486, compound

HRID 46266Notes

Reaction equation

HRID 46266 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([S:10]([NH:13][C:14]2[S:18][N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([OH:45])=[C:24]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([N:32]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]3)[N:27]=2)[CH:25]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O.[Cl-].[NH4+]>>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([O:45][C:8]2[CH:7]=[CH:6][C:5]([S:10]([NH:13][C:14]3[S:18][N:17]=[CH:16][N:15]=3)(=[O:12])=[O:11])=[CH:4][C:3]=2[C:1]#[N:2])=[C:24]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([N:32]3[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39])[CH2:36][CH2:37]3)[N:27]=2)[CH:25]=1

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 580423023-cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 1357436831,1-Dimethylethyl 4-(4-(5-chloro-2-hydroxyphenyl)-2-pyrimidinyl)-1-piperazinecarboxylate

Product 1

HCID 66905486HCID 66905486, compound

Procedure

3-Cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (Preparation 65, 43.6 mg, 0.154 mmol), tert-butyl 4-[4-(5-chloro-2-hydroxyphenyl)pyrimidin-2-yl]piperazine-1-carboxylate (Preparation 873, 50.0 mg, 0.128 mmol) and potassium carbonate (53 mg, 0.38 mmol) in dimethyl sulfoxide (1 mL, 10 mmol) was stirred at 100° C. for 16 hours. The reaction mixture was cooled to ambient temperature and poured into saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude intermediate, tert-butyl 4-[4-(5-chloro-2-{2-cyano-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]phenoxy}phenyl)pyrimidin-2-yl]piperazine-1-carboxylate, as a yellow solid. Trifluoroacetic acid (300 uL, 4 mmol) was added to a solution of tert-butyl 4-[4-(5-chloro-2-{2-cyano-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]phenoxy}phenyl)pyrimidin-2-yl]piperazine-1-carboxylate (83 mg, 0.154 mmol) in methylene chloride (2.9 mL, 46 mmol). After 1 hour, the reaction mixture was concentrated in vacuo. The residue was purified by reverse-phase HPLC to afford the product as a white solid (trifluoroacetic acid salt, 36 mg, 51%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2c9581348814e32833b2972dcd880a7
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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