Trifluoroacetic acid → 6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516008Notes

Reaction equation

HRID 516008 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[CH2:14][C:13]2[C:12]([F:15])=[C:11]([NH:16][C@@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]3[NH:23]C(=O)OC(C)(C)C)[N:10]=[C:9]([C:31]3[CH:32]=[N:33][N:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=34)[C:8]=2[C:7]1=[O:40].C(O)(C(F)(F)F)=O>>[NH2:23][C@H:18]1[CH2:19][CH2:20][CH2:21][CH2:22][C@H:17]1[NH:16][C:11]1[N:10]=[C:9]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)[C:8]2[C:7](=[O:40])[NH:6][CH2:14][C:13]=2[C:12]=1[F:15]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654714tert-butyl (1S,2R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-4-(pyrazolo[1,5-a]pyridin-3-yl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 1

HCID 532522796-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 48.1%

Conditions

Temperature
65 °C

Procedure

A mixture of tert-butyl (1S,2R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-4-(pyrazolo[1,5-a]pyridin-3-yl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (52 mg, 0.082 mmol) and TFA (1 mL, 12.98 mmol) was stirred at 65° C. for 30 min. The mixture was concentrated and the residue was purified by preparative HPLC to give the title compound as a white solid (15 mg, 47.8%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.21-2.07 (m, 8 H), 3.31 (br s, 1 H), 4.18-4.26 (m, 1 H), 4.46 (br s, 2 H), 6.61 (br s, 1 H), 7.09 (d, J=6.35 Hz, 1 H), 7.49 (d, J=7.32, 1 H), 8.36 (br s, 1 H), 8.59 (d, J=7.81 Hz, 1 H), 8.83 (d, J=6.83 Hz, 1 H), 9.56 (br s, 1 H). [M+H] calc'd for C20H21FN6O, 381; found, 381.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-83c5dbbdf2734b8f9b929b45383c8aec
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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