Sodium Hydroxide → 5-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid
Reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:21]=[N:22][CH:23]=2)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][C:13]=1[F:20])=[O:4].[OH-].[Na+]>>[F:20][C:13]1[CH:14]=[C:15]([S:18][CH3:19])[CH:16]=[CH:17][C:12]=1[NH:11][C:10]1[N:9]2[CH:21]=[N:22][CH:23]=[C:8]2[CH:7]=[CH:6][C:5]=1[C:3]([OH:4])=[O:2]Participants
Conditions
- Temperature
- 65 °C
Procedure
To a solution of 5-(2-fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester (150 mg, 0.45 mmol) in IMS (10 mL) was added sodium hydroxide (0.5 mL, 1M aqueous solution, 0.5 mmol), the reaction mixture heated at 65° C. for 1.5 hours. The reaction mixture was concentrated in vacuo then taken up in water (ca. 15 mL), the aqueous solution was washed with diethyl ether before the pH was adjusted to pH 3 using 1M HCl, resulting in precipitation of a brown solid. The precipitate was extracted using ethyl acetate, the organic phase was isolated and washed with water followed by brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford the title compound as a brown solid (109 mg, 76%). 1H NMR (CD3OD): 7.67 (1H, s), 7.44 (1H, d, J=9.53 Hz), 7.39 (1H, d, J=0.83 Hz), 7.24 (1H, dd, J=9.57, 0.80 Hz), 7.15 (1H, dd, J=11.47, 2.12 Hz), 7.02-7.01 (1H, m), 6.76 (1H, t, J=8.49 Hz), 2.49 (3H, s).
Workup
- concentrationThe reaction mixture was concentrated in vacuo
- washthe aqueous solution was washed with diethyl ether before the pH
- customresulting in precipitation of a brown solid
- extractionThe precipitate was extracted
- customthe organic phase was isolated
- washwashed with water
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-ab903aba27ea435b8cc69dc7a5e299be
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07923456B2
Reaction notes
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