Benzenesulfonyl chloride → 1-Benzenesulfonyl-5-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

HRID 60229Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([Cl:14])[CH:12]=2)[NH:7][C:6]=1[CH3:15])=[O:4].[OH-].[Na+].[C:18]1([S:24](Cl)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.ClCCl>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([Cl:14])[CH:12]=2)[N:7]([S:24]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:26])=[O:25])[C:6]=1[CH3:15])=[O:4]

Participants

Conditions

Temperature: 2.5 °C

Procedure

A cooled (0-5° C.) suspension of 5-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (57 g, 0.25 mol), powdered sodium hydroxide (30.45 g, 0.76 mol) and benzyltriethylammonium chloride (1.16 g, 5.1 mmol) in dichloromethane (800 mL) was treated over ca. 5 minutes with benzenesulfonyl chloride (56.1 g, 40.5 mL, 0.32 mol). The reaction mixture was allowed to stir at 0-5° C. for 15 minutes then allowed to warm to ambient temperature and stirred for 24 hours. The solid was removed by filtration through celite and the cake washed with dichloromethane. The filtrate was evaporated and the resultant residue triturated with diethyl ether to afford the title compound as a brown solid (17.5 g, 30%). LCMS (Method B): RT=4.67 min, M+Na+=381. 1H NMR (400 MHz, CDCl3): 8.34 (d, J=2.4 Hz, 1H), 8.25 (d, J=2.4 Hz, 1H), 8.18-8.18 (m, 2H), 7.61-7.61 (m, 1H), 7.51-7.50 (m, 2H), 3.94 (s, 3H), 3.15 (s, 3H).

Workup

temperatureA cooled
temperatureto warm to ambient temperature
stirringstirred for 24 hours
customThe solid was removed by filtration through celite
washthe cake washed with dichloromethane
customThe filtrate was evaporated
customthe resultant residue triturated with diethyl ether

Sources & evidence

ORD record: ord-19931c1cc2264654b8ded6339bf72c73
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

Loading…