Acetic Anhydride → HCID 66664340, compound

HRID 1892980Notes

Reaction equation

HRID 1892980 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]([CH:19]([F:21])[F:20])[CH:15]=[CH:16][CH:17]=3)[C:12]([N:22]([S:32]([C:35]3[S:36][C:37]([Cl:40])=[CH:38][CH:39]=3)(=[O:34])=[O:33])[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.C(N(CC)CC)C.[C:48](OC(=O)C)(=[O:50])[CH3:49]>ClCCl>[Cl:31][C:28]1[S:27][C:26]([S:23]([N:22]([S:32]([C:35]2[S:36][C:37]([Cl:40])=[CH:38][CH:39]=2)(=[O:33])=[O:34])[C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][C:14]=3[CH:19]([F:20])[F:21])[N:10]([CH2:9][C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:48](=[O:50])[CH3:49])[CH:8]=[CH:7][CH:6]=3)[N:11]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 58054526HCID 58054526, compound

Product 1

HCID 66664340HCID 66664340, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(difluoromethyl)-1H-indazol-3-yl]-5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-2-thiophenesulfonamide (for a preparation see Intermediate 70) (26 mg, 0.039 mmol) was suspended in dichloromethane (0.5 mL) and triethylamine (0.055 mL, 0.39 mmol) and then acetic anhydride (0.004 mL, 0.043 mmol) was added to the suspension. The mixture was stirred for 1 h, and concentrated under a stream of nitrogen to give N-[(3-{[3-{Bis[(5-chloro-2-thienyl)sulfonyl]amino}-4-(difluoromethyl)-1H-indazol-1-yl]methyl}phenyl)methyl]acetamide, which was used without further purification. The residue was dissolved in methanol (2 mL) and treated with NaOH (0.553 mL, 1.105 mmol) and the reaction mixture was stirred at 60° C. for 3 h. LCMS showed the reaction had gone to completion so the mixture was concentrated in vacuo and acidified with 5% citric acid. The solution was extracted with ethyl acetate and the organic layer was washed twice with water (25 mL) and once with brine (25 mL). The organic layer was dried over anhydrous magnesium sulfate before being evaporated in vacuo to give a yellow residue which was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier (Method A). The solvent was evaporated in vacuo to give the title compound (7 mg, 36%). LCMS (System A) RT=1.02 min, ES+ve m/z 525/527 (M+H)+.

Workup

  1. concentrationconcentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-5a46032c403c423198c7bd21251ed94c
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

Loading…