Hydrochloric Acid → 1-[8-Chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-yl]ethanone
Reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([CH:21]=[N:22][CH:23]=2)[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:6]([C:8](N(OC)C)=[O:9])[CH:7]=1.[CH3:24][Mg]Br.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[Cl:1][C:2]1[C:3]2[N:4]([CH:21]=[N:22][CH:23]=2)[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:6]([C:8](=[O:9])[CH3:24])[CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
8-Chloro-5-(3-fluorophenyl)-N-methoxy-N-methylimidazo[1,5-a]pyridine-6-carboxamide (0.15 g, 0.45 mmol) was stirred in tetrahydrofuran (0.73 mL) and cooled to 0° C. A solution of 3.0 M methylmagnesium bromide (0.52 mL, 1.57 mmol) was added dropwise. The mixture was stirred at 0° C. for 30 minutes and at room temperature for 1 hour. The mixture was cooled to 0° C. and a solution of 1.0 M hydrogen chloride in water (1.8 mL) was added. The mixture was poured into saturated sodium bicarbonate and extracted into ethyl acetate 3×. The ethyl acetate extracts were combined and washed with water, dried over sodium sulfate, filtered, concentrated and purified by flash column chromatography with ethyl acetate in hexanes (0-80%) to give the desired compound (0.12 g, 93%). LCMS calculated for C15H11ClFN2O (M+H)+: m/z=289.1. found: 288.9. 1H NMR (300 MHz, DMSO-d6): δ 7.89 (s, 1H), 7.62 (m, 2H), 7.50 (m, 2H), 7.40 (m, 2H), 2.10 (s, 3H).
Workup
- temperatureThe mixture was cooled to 0° C.
- extractionextracted into ethyl acetate 3×
- washwashed with water
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- custompurified by flash column chromatography with ethyl acetate in hexanes (0-80%)
Sources & evidence
- ORD record
- ord-be9ada9934f14aca89b34d11d9d10f9e
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09193721B2
Reaction notes
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