Trifluoroacetic acid → Mivavotinib

HRID 711465Notes

Reaction equation

HRID 711465 reaction equation
[F:1][C:2]1[C:3]2[CH2:31][NH:30][C:29](=[O:32])[C:4]=2[C:5]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15]C(=O)OC(C)(C)C.[C:33]([OH:39])([C:35]([F:38])([F:37])[F:36])=[O:34]>C(Cl)Cl>[C:33]([OH:39])([C:35]([F:38])([F:37])[F:36])=[O:34].[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:7]1[N:6]=[C:5]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)[C:4]2[C:29](=[O:32])[NH:30][CH2:31][C:3]=2[C:2]=1[F:1]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654710tert-butyl (1S,2R)-2-(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 53252276MivavotinibYield 60.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (1S,2R)-2-(7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (15 mg, 0.034 mmol) and TFA (0.5 mL, 6.49 mmol) in DCM (0.5 mL) was stirred at RT for 30 min. The reaction mixture was concentrated and the resulting residue was purified by preparative HPLC to give a TFA salt of the title compound (7 mg, 60.2%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.37-2.01 (m, 8H), 3.67 (br s, 1H), 3.89 (s, 3H), 4.32-4.43 (m, 2H), 4.45 (br s, 1H), 6.77 (d, J=6.35 Hz, 1H), 7.93 (br s, 3H), 8.30 (s, 1H), 8.36 (s, 1H), 8.84 (s, 1H). [M+H] calc'd for C17H21FN6O, 345. found, 345.

Workup

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

Sources & evidence

ORD record
ord-e70c2ad71b0745b1ac4923e032569e88
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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