Hydrogen Bromide → 6-((1R,2S)-2-Aminocyclohexylamino)-4-bromo-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516119Notes

Reaction equation

Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9](CC3C=CC(OC)=CC=3OC)[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31]C(=O)OC(C)(C)C)[N:3]=1.[BrH:39]>CC(O)=O>[NH2:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]1[NH:24][C:4]1[N:3]=[C:2]([Br:39])[C:7]2[C:8](=[O:22])[NH:9][CH2:10][C:6]=2[C:5]=1[F:23]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (200 mg, 0.364 mmol) and hydrobromic acid in HOAc (10 mL) was stirred at 90° C. for 6 h. The mixture was concentrated under reduced pressure, and the resulting crude material was reconstituted in MeOH (1.0 mL) and was purified via preparative HPLC eluting with water (0.05% TFA) and ACN (15-30% gradient, 0.035% TFA). The collected fractions were combined and ACN was removed via rotary evaporation. The resulting aqueous solution was neutralized with saturated aqueous NaHCO3, washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to yield the title compound (38 mg, 30%). [M+H] calc'd for C13H16BrFN4O, 343; found, 343.

Workup

concentrationThe mixture was concentrated under reduced pressure
customwas purified via preparative HPLC
washeluting with water (0.05% TFA) and ACN (15-30% gradient, 0.035% TFA)
customACN was removed via rotary evaporation
washwashed with EtOAc (2×200 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customThe organic phase was stripped to dryness via rotary evaporation

Sources & evidence

ORD record: ord-770a2ee274244303918a36ddb32ae118
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108970B2

Reaction notes

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