Dichloromethane → 4-[4-Chloro-2-(2-piperazin-1-ylpyrimidin-4-yl)phenoxy]-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 1401934Notes

Reaction equation

FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([O:34][C:35]2[CH:40]=[CH:39][C:38]([S:41]([NH:44][C:45]3[S:49][N:48]=[CH:47][N:46]=3)(=[O:43])=[O:42])=[CH:37][C:36]=2[C:50]#[N:51])=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]3)[N:16]=2)[CH:14]=1.C(Cl)Cl>>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([O:34][C:35]2[CH:40]=[CH:39][C:38]([S:41]([NH:44][C:45]3[S:49][N:48]=[CH:47][N:46]=3)(=[O:42])=[O:43])=[CH:37][C:36]=2[C:50]#[N:51])=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:16]=2)[CH:14]=1

Participants

Reactant 3

HCID 6344Dichloromethane

HCID 6422Trifluoroacetic acid

HCID 66905486Tert-butyl 4-[4-(5-chloro-2-{2-cyano-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]phenoxy}phenyl)pyrimidin-2-yl]piperazine-1-carboxylate

Product 1

HCID 468417904-[4-Chloro-2-(2-piperazin-1-ylpyrimidin-4-yl)phenoxy]-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamideYield 51%

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

concentrationthe reaction mixture was concentrated in vacuo
customThe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record: ord-8125e3c31db94f4e8c8af6488987315d
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08907101B2

Reaction notes

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