tert-butyl ({4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-3-cyanophenyl}sulfonyl)1,3-thiazol-4-ylcarbamate → 4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-3-cyano-N-1,3-thiazol-4-ylbenzenesulfonamide

HRID 46254Notes

Reaction equation

HRID 46254 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]([C:10]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:11]=3[O:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([N:22]([C:30]4[N:31]=[CH:32][S:33][CH:34]=4)C(=O)OC(C)(C)C)(=[O:21])=[O:20])=[CH:15][C:14]=3[C:35]#[N:36])=[CH:8][CH:7]=[N:6]2)[CH2:2]1>Cl.O1CCOCC1>[NH:1]1[CH2:2][CH:3]([N:5]2[C:9]([C:10]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:11]=3[O:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH:22][C:30]4[N:31]=[CH:32][S:33][CH:34]=4)(=[O:21])=[O:20])=[CH:15][C:14]=3[C:35]#[N:36])=[CH:8][CH:7]=[N:6]2)[CH2:4]1

Participants

4

Reactant 1

HCID 59436550tert-butyl ({4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-3-cyanophenyl}sulfonyl)1,3-thiazol-4-ylcarbamate

Product 1

HCID 574948254-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-3-cyano-N-1,3-thiazol-4-ylbenzenesulfonamideYield 38.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-butyl ({4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-3-cyanophenyl}sulfonyl)1,3-thiazol-4-ylcarbamate (Preparation 679, 200 mg, 0.326 mmol) was stirred in 4M hydrogen chloride solution in 1,4-dioxan (10 ml) at room temperature for 2 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between methyl-t-butyl ether (80 ml) and water (40 ml). The aqueous layer was neutralized to pH=7 by adding sodium hydrogen carbonate and was then concentrated in vacuo. The crude product was purified by column chromatography on silica gel using dichloromethane:methanol:0.880 aqueous ammonia, 90:10:1 to 70:30:3. This gave a buff powder (65 mg) which was triturated with methyl tert-butyl ether to give the title compound as a buff powder, 55 mg.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between methyl-t-butyl ether (80 ml) and water (40 ml)
  3. additionby adding sodium hydrogen carbonate
  4. concentrationwas then concentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c6b01721358f484e8bdc1c9cf0fb4e01
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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