Trifluoroacetic acid → Trifluoroacetic acid

HRID 711524Notes

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]>>[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].[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45]

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 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 acid

HCID 53252276Mivavotinib

Procedure

A solution of cis-tert-butyl 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 (109 mg, 0.183 mmol) in TFA (5 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 give the title compound as a TFA salt. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.47 (br s, 2H), 1.57-1.75 (m, 3H), 1.84 (br s, 2H), 3.12-3.23 (m, 2H), 3.87-3.94 (m, 3H), 4.35-4.50 (m, 3H), 6.73 (br s, 1H), 7.71 (br s, 2H), 8.28-8.44 (m, 2H), 8.84 (d, J=3.91 Hz, 1H). [M+H] calc'd for C17H21FN6O, 345. found, 345.

Workup

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

Sources & evidence

ORD record: ord-f9cf6e63c9084e49a3cde0bfc4e259cb
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181255B2

Reaction notes

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