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

HRID 711501Notes

Reaction equation

HRID 711501 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]([CH3:36])[CH:35]=3)[C:8]=2[C:7]1=[O:37].[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45]>>[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45].[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]([CH3:36])[CH:35]=2)[C:8]2[C:7](=[O:37])[NH:6][CH2:14][C:13]=2[C:12]=1[F:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67238656tert-Butyl (1R,2S)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 532502176-((1S,2R)-2-Aminocyclohexylamino)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 92%

Conditions

Temperature
65 °C

Procedure

A mixture of tert-butyl (1R,2S)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (41.5 mg, 0.070 mmol) and TFA (2 mL) was heated at 65° C. for 3 h. Following reaction, the solvent was removed in vacuo. The residue was diluted with DMSO and MeOH (1/1), passed through a microfiltration frit, and purified via preparative HPLC. The fractions were collected and dried in vacuo to give a TFA salt of the title compound as a white solid (22 mg, 92%). 1H NMR (500 MHz, CD3OD) δ ppm 1.56-2.01 (m, 8H), 3.85 (br s, 1H), 3.94 (br s, 3H), 4.45 (br s, 2H), 4.67 (br s, 1H), 8.31 (br s, 1H), 8.81 (br s, 1H). [M+H] calc'd for C17H21FN6O, 345. found, 345.

Workup

  1. customreaction
  2. customthe solvent was removed in vacuo
  3. additionThe residue was diluted with DMSO and MeOH (1/1)
  4. custompurified via preparative HPLC
  5. customThe fractions were collected
  6. customdried in vacuo

Sources & evidence

ORD record
ord-f3c6cdc2e4bb43178809b60e3c80a510
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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