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Trifluoroacetic acid → Trifluoroacetic acid

HRID 711521
Notes
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Reaction equation

HRID 711521 reaction equation
[F:1][CH:2]([F:45])[N:3]1[CH:7]=[C:6]([C:8]2[C:13]3[C:14](=[O:28])[N:15](CC4C=CC(OC)=CC=4OC)[CH2:16][C:12]=3[C:11]([F:29])=[C:10]([NH:30][C@@H:31]3[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]3[NH:37]C(=O)OC(C)(C)C)[N:9]=2)[CH:5]=[N:4]1.[C:46]([OH:52])([C:48]([F:51])([F:50])[F:49])=[O:47]>>[NH2:37][C@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]1[NH:30][C:10]1[N:9]=[C:8]([C:6]2[CH:5]=[N:4][N:3]([CH:2]([F:1])[F:45])[CH:7]=2)[C:13]2[C:14](=[O:28])[NH:15][CH2:16][C:12]=2[C:11]=1[F:29].[C:46]([OH:52])([C:48]([F:51])([F:50])[F:49])=[O:47]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654725tert-Butyl (1S,2R)-2-(4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 2

HCID 6422Trifluoroacetic acidYield 86%HCID 532503696-((1R,2S)-2-Aminocyclohexylamino)-4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Procedure

A solution of tert-butyl (1S,2R)-2-(4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (36 mg, 0.057 mmol) in TFA (2 mL) was heated at 60° C. for 2 h. After removal of the solvent, the residue was diluted in MeOH (2 mL) and was purified by preparative HPLC. The fractions were collected and stripped to dryness via rotary evaporation to yield the title compound as a TFA salt (18.7 mg, 86%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.40-1.52 (m, 2H), 1.58-1.76 (m, 3H), 1.75-1.94 (m, 3H), 3.67 (br s, 1H), 4.44 (d, J=4.88 Hz, 2H), 4.53 (br s, 1H), 6.86 (d, J=6.83 Hz, 1H), 7.71 (br s, 2H), 7.79-8.12 (m, 1H), 8.53 (s, 2H), 9.41 (s, 1H). [M+H] calc'd for C17H19F3N6O, 381. found, 381.

Workup

  1. customAfter removal of the solvent
  2. additionthe residue was diluted in MeOH (2 mL)
  3. customwas purified by preparative HPLC
  4. customThe fractions were collected
  5. customstripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-7960c56cd9144577ab684f732668a3e8
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09181255B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes