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

HRID 516069Notes

Reaction equation

HRID 516069 reaction equation
[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:16]=[C:15]([C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)[C:14]2[C:23](=[O:37])[N:24](CC3C=CC(OC)=CC=3OC)[CH2:25][C:13]=2[C:12]=1[F:38].[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40]>C(Cl)Cl>[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40].[NH2:1][C@H:2]1[C:7]([F:8])([F:9])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:16]=[C:15]([C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)[C:14]2[C:23](=[O:37])[NH:24][CH2:25][C:13]=2[C:12]=1[F:38]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 672390206-(cis-2-Amino-3,3-difluorocyclohexylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Product 2

HCID 6422Trifluoroacetic acidHCID 532505196-(cis-2-Amino-3,3-difluorocyclohexylamino)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 23.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(cis-2-amino-3,3-difluorocyclohexylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (21 mg, 0.040 mmol) in DCM (300 μL) was added TFA (500 μL, 6.49 mmol). The reaction mixture was stirred at ambient temperature for 12 h then an additional 3 h at 50° C. The mixture was subsequently concentrated to a dark oil and diluted with DMF (1 mL) which was purified via preparative HPLC and lyophilized to give a TFA salt of the title compound as a fluffy white solid (3.6 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.89 (s, 1 H), 8.43 (s, 3 H), 8.16 (s, 1 H), 6.89 (br s, 1 H), 6.54 (br s, 1 H), 4.65-4.52 (m, 1 H), 4.49-4.32 (m, 2 H), 4.17 (br s, 1 H), 3.89 (s, 3 H), 2.37-2.03 (m, 2 H), 1.84 (br s, 3 H), 1.63 (br s, 1 H). [M+H] calc'd for C17H19F3N6O, 381; found, 381.

Workup

  1. customan additional 3 h
  2. customat 50° C
  3. concentrationThe mixture was subsequently concentrated to a dark oil
  4. additiondiluted with DMF (1 mL) which
  5. customwas purified via preparative HPLC

Sources & evidence

ORD record
ord-3b9408b1de674ca69fff63af497772f4
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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