Hydrochloric Acid → methyl 2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate

HRID 1473217Notes

Reaction equation

[OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[NH:15][CH:16]=[CH:17][C:9]=2[C:8]=1[C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)[C:3]([O:5][CH3:6])=[O:4].[C:25]([O-])([O-])=O.[Cs+].[Cs+].CI.Cl>C(#N)C.O>[CH3:25][N:15]1[C:10]2[C:11](=[O:14])[N:12]([CH3:13])[C:7]([CH:2]([OH:1])[C:3]([O:5][CH3:6])=[O:4])=[C:8]([C:18]3[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=3)[C:9]=2[CH:17]=[CH:16]1

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of methyl 2-hydroxy-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (30 mg, 0.092 mmol) and Cs2CO3 (35.9 mg, 0.110 mmol) in Acetonitrile (1 mL) was treated with MeI (6.90 μL, 0.110 mmol) and heated to 50° C. for 3 hours. Additional MeI (10 uL) was added, the reaction was stirred at 50° C. for 3 hours. The mixture was cooled to rt, diluted with water, acidified with 1N HCl, extracted with EtOAc 3×, washed with brine, dried with Na2SO4, filtered, and concentrated. Combined with crude product from the same reaction (0.040 mol scale) and purified with column chromatography (0-100% EtOAc/Hexane) to give methyl 2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (31.7 mg, 0.093 mmol, 70.6% yield) as clear oil. LCMS (m/z) ES+=341 (M+1).

Workup

temperatureThe mixture was cooled to rt
extractionextracted with EtOAc 3×
washwashed with brine
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated
customCombined with crude product from the same reaction (0.040 mol scale)
custompurified with column chromatography (0-100% EtOAc/Hexane)

Sources & evidence

ORD record: ord-a6779ed0b8aa4047a843fd15aa44eeee
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012642B2

Reaction notes

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