Pyridine → HCID 59456026, compound

HRID 1808637Notes

Reaction equation

HRID 1808637 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([O:20][CH3:21])[C:15]([F:19])=[CH:16][CH:17]=3)[C:12]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:11]2)[CH:6]=[CH:7][CH:8]=1.N1C=CC=CC=1.[OH-].[K+].C([O:43][C:44]([CH3:49])([CH3:48])[C:45](Cl)=[O:46])(=O)C>ClCCl>[Cl:31][C:28]1[S:27][C:26]([S:23]([NH:22][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[O:20][CH3:21])[N:10]([CH2:9][C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:45](=[O:46])[C:44]([OH:43])([CH3:49])[CH3:48])[CH:8]=[CH:7][CH:6]=3)[N:11]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 14797Potassium HydroxideHCID 1234962-Acetoxyisobutyroyl chlorideHCID 59455989N-[1-{[3-(Aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Product 1

HCID 59456026HCID 59456026, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 61) (100 mg, 0.208 mmol) in dichloromethane (0.5 mL),pyridine (0.5 mL) and potassium hydroxide (11.67 mg, 0.208 mmol) was treated with 2-chloro-1,1-dimethyl-2-oxoethyl acetate (0.054 mL, 0.37 mmol) and the mixture was stirred for 2.5 h. The reaction mixture was concentrated in vacuo and the orange residue was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a TFA modifier (Method B). The solvent was evaporated in vacuo to give the title compound (58 mg, 49%). LCMS (System A) RT=1.04 min, ES+ve m/z 567/569 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe orange residue was dissolved in 1:1 MeOH-DMSO (1 mL)
  3. custompurified by Mass Directed AutoPrep on Sunfire C18 column
  4. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-abfe4a853f354faab7678465fcd76bf4
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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