Pyridine → 5-Chloro-N-[4-methoxy-1-[[3-[[(methylsulfonyl)amino]methyl]phenyl]methyl]-1H-indazol-3-yl]-2-thiophenesulfonamide

HRID 1808604Notes

Reaction equation

HRID 1808604 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34].N1C=CC=CC=1>C(Cl)Cl>[Cl:31][C:28]1[S:27][C:26]([S:23]([NH:22][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[N:11]([CH2:10][C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([CH2:3][NH:2][S:33]([CH3:32])(=[O:35])=[O:34])[CH:5]=3)[N:12]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 66632476N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride

Product 1

HCID 580544295-Chloro-N-[4-methoxy-1-[[3-[[(methylsulfonyl)amino]methyl]phenyl]methyl]-1H-indazol-3-yl]-2-thiophenesulfonamideYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride ((for a preparation see Intermediate 4) 51 mg, 0.10 mmol) in dry DCM (3 mL) was added methanesulfonyl chloride (8 μL, 0.1 mmol), followed by pyridine (1 mL). The resultant pale yellow solution was stirred at room temperature overnight. LCMS showed only 19% of required product. Triethylamine (14 μL, 0.10 mmol), followed by more methanesulfonyl chloride (8 μL, 0.1 mmol) were added and stirring was continued for a further 30 min. The reaction mixture was then concentrated in vacuo and the residue dissolved in 1:1 MeOH:DMSO (1 mL) and purified by MDAP (supelcosil ABZ+Plus column) eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid). The solvent was evaporated in vacuo to give the title product (10.7 mg, 19%) as a white solid. LCMS (System A) RT=1.13 min, ES+ve m/z 541/543 (M+H)+.

Sources & evidence

ORD record
ord-5283b688bbdb4d55b09099117e7fa9a5
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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