Trifluoroacetic acid → Mivavotinib

HRID 516000Notes

Reaction equation

HRID 516000 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, 8 H), 3.67 (br s, 1 H), 3.89 (s, 3 H), 4.32-4.43 (m, 2 H), 4.45 (br s, 1 H), 6.77 (d, J=6.35 Hz, 1 H), 7.93 (br s, 3 H), 8.30 (s, 1 H), 8.36 (s, 1 H), 8.84 (s, 1 H). [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-fc4809769d624734aaf202fd3f44b453
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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