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 1692218Notes

Reaction equation

HRID 1692218 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-4568e82baf4e42a98f62662dc991b642
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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