5-Chlorothiophene-2-sulfonyl chloride → 5-Chloro-N-{1-[(3-cyanophenyl)methyl]-4-fluoro-1H-indazol-3-yl}-2-thiophenesulfonamide

HRID 1808575Notes

Reaction equation

HRID 1808575 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[N:4]([CH2:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[C:16]#[N:17])[N:3]=1.[Cl:21][C:22]1[S:26][C:25]([S:27](Cl)(=[O:29])=[O:28])=[CH:24][CH:23]=1>N1C=CC=CC=1>[Cl:21][C:22]1[S:26][C:25]([S:27]([NH:1][C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[F:11])[N:4]([CH2:12][C:13]3[CH:20]=[CH:19][CH:18]=[C:15]([C:16]#[N:17])[CH:14]=3)[N:3]=2)(=[O:29])=[O:28])=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 580543733-[(3-Amino-4-fluoro-1H-indazol-1-yl)methyl]benzonitrile

Product 1

HCID 580545775-Chloro-N-{1-[(3-cyanophenyl)methyl]-4-fluoro-1H-indazol-3-yl}-2-thiophenesulfonamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 3-[(3-amino-4-fluoro-1H-indazol-1-yl)methyl]benzonitrile (for a preparation see Intermediate 37) (695 mg, 2.61 mmol) in anhydrous pyridine (3 mL) cooled in an ice/water bath was added 5-chloro-2-thiophenesulfonyl chloride (567 mg, 2.61 mmol) dropwise over 1 minute and the reaction mixture was stirred in the ice/water bath for 1 hour. The reaction mixture was partitioned between ethyl acetate (150 mL) and 2N hydrochloric acid (100 mL). The organic layer was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a dark red oil (1.264 g). The oil was dissolved in the minimum volume of dichloromethane, applied to a 100 g silica SPE cartridge and purified by chromatography on Flashmaster II using a 0-50% ethyl acetate in cyclohexane gradient over 60 min. Fractions 66-69 were combined and evaporated in-vacuo to yield a white foam (540 mg), which was further purified by chromatography on 100 g silica SPE cartridge on Flashmaster II using a 0-10% methanol in dichloromethane gradient over 60 min. Fractions 23-26 were evaporated in-vacuo to yield the title compound as a white foam (493 mg, 42%). LCMS (System B) RT=3.01 min, ES+ve m/z 447/449 (M+H)+.

Workup

  1. temperaturecooled in an ice/water bath
  2. customThe reaction mixture was partitioned between ethyl acetate (150 mL) and 2N hydrochloric acid (100 mL)
  3. customThe organic layer was separated
  4. customevaporated in-vacuo

Sources & evidence

ORD record
ord-9304f5093127426b8b8ae678b80051e7
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

Loading…