Hydrochloric Acid → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246570Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([O:23]C)=[O:22])=[CH:19][N:18]([CH2:25][O:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[OH-].[K+].O.Cl>O1CCOCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=[O:22])=[CH:19][N:18]([CH2:25][O:26][C:27](=[O:32])[C:28]([CH3:30])([CH3:29])[CH3:31])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate (0.24 g, 0.546 mmol), KOH (0.611 g, 10.9 mmol), water (4 mL) and dioxane (10 mL) was stirred at 100° C. for 5 hours. Then the reaction mixture was cooled to room temperature and treated with 1N HCl to pH=2. The solvent was evaporated at 40° C. under reduced pressure and the residue was triturated with water (10 mL), then decanted and dried at 40° C. under reduced pressure to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.161 g, 94.8%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 12.87 (s, 1H), 12.28 (s, 1H), 9.05 (s, 1H), 8.82 (dd, 1H, J1=9.0 Hz, J2=5.7 Hz), 8.48 (d, 1H, J=2.7 Hz), 7.61 (dd, 1H, J1=10.2 Hz, J2=2.7 Hz), 7.15 (t, 1H, J=12.0 Hz), 4.12 (s, 3H). LCMS: 312.0 [M+H]+, 334.0 [M+Na]+.

Workup

temperatureThen the reaction mixture was cooled to room temperature
customThe solvent was evaporated at 40° C. under reduced pressure
customthe residue was triturated with water (10 mL)
customdecanted
customdried at 40° C. under reduced pressure

Sources & evidence

ORD record: ord-25ba025e2b7745bfb11f4c51e2e9b81f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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