Benzenesulfonamide → 6-Chloro-5-(4-methoxyphenyl)-N-(phenylsulfonyl)-1H-indazole-3-carboxamide

HRID 338481Notes

Reaction equation

HRID 338481 reaction equation
[C:1]1([S:7]([NH2:10])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].C1(C)C=CC([O:23][C:24]([C:26]2[C:34]3[C:29](=[CH:30][C:31]([Cl:43])=[C:32]([C:35]4[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=4)[CH:33]=3)[NH:28][N:27]=2)=O)=CC=1>C1COCC1>[Cl:43][C:31]1[CH:30]=[C:29]2[C:34]([C:26]([C:24]([NH:10][S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])=[O:23])=[N:27][NH:28]2)=[CH:33][C:32]=1[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 7370BenzenesulfonamideHCID 23665647Potassium tert-butoxideHCID 866988166-Chloro-5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid p-tolyl ester

Product 1

HCID 866988176-Chloro-5-(4-methoxyphenyl)-N-(phenylsulfonyl)-1H-indazole-3-carboxamideYield 3.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of benzenesulfonamide (25.6 mg, 0.163 mmol) and potassium tert-butoxide (22.0 mg, 0.196 mmol) in THF (10 mL) was stirred for 10 minutes, and treated with 6-chloro-5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid p-tolyl ester (64 mg, 0.16 mmol). The reaction mixture was heated to 65° C. for 16 hours, cooled to room temperature and concentrated in vacuo. The residue was partitioned between water (5 mL) and EtOAc (5 mL), and the layers were separated. The organic layer was concentrated in vacuo and the crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 60:40 A:B linear to 30:70 A:B in 8.5 min to 100% B to 9.0 min, hold at 100% B from 9.0 to 10.0 min. Flow: 25 mL/min) to give the title compound (2.2 mg, 3% yield). MS (ES+) 442.0 (M+1)+. Retention time=3.29 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between water (5 mL) and EtOAc (5 mL)
  4. customthe layers were separated
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe crude material was purified by reverse phase HPLC (Column
  7. waitGradient: 60:40 A:B linear to 30:70 A:B in 8.5 min to 100% B to 9.0 min
  8. waithold at 100% B from 9.0 to 10.0 min

Sources & evidence

ORD record
ord-57f802d390f148fd990c69f05163411f
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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