Trifluoroacetic acid → 8-(2,4-Difluorophenoxy)-7-(6-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)quinoxalin-2(1H)-one

HRID 1056979Notes

Reaction equation

HRID 1056979 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:10]=1[O:11][C:12]1[C:13]([C:23]2[C:24]3[CH:33]=[N:32][N:31](COCC[Si](C)(C)C)[C:25]=3[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=2)=[CH:14][CH:15]=[C:16]2[C:21]=1[NH:20][C:19](=[O:22])[CH2:18][NH:17]2>C(Cl)Cl>[F:8][C:9]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:10]=1[O:11][C:12]1[C:13]([C:23]2[C:24]3[CH:33]=[N:32][NH:31][C:25]=3[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=2)=[CH:14][CH:15]=[C:16]2[C:21]=1[NH:20][C:19](=[O:22])[CH:18]=[N:17]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 1232172868-(2,4-Difluorophenoxy)-7-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one

Product 1

HCID 1180939868-(2,4-Difluorophenoxy)-7-(6-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)quinoxalin-2(1H)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.40 mL, 5.19 mmol) was added dropwise at RT to a solution of 8-(2,4-difluorophenoxy)-7-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-4-yl)-3,4-dihydroquinoxalin-2(1H)-one (10.5 mg, 0.0190 mmol, mixture of oxidized (quinoxalin) and reduced (dihydroquinoxalin) forms from previous step) in methylene chloride (0.40 mL), and the reaction mixture was stirred at RT for 1 h. The reaction mixture was purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (4 mg, 50%). 1H NMR (500 MHz, DMSO-d6) δ 14.05 (br s, 1H), 12.50 (br s, 1H), 8.19 (s, 1H), 7.79 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.3 Hz, 1H), 7.35 (s, 1H), 7.16-6.99 (m, 1H), 6.70-6.56 (m, 1H), 6.55-6.34 (m, 1H), 3.48 (s, 3H); LCMS calculated for C21H14F2N5O3 (M+H)+: m/z=422.1. found: 422.0.

Workup

  1. customThe reaction mixture was purified via preparative LCMS (XBridge C18 column
  2. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-8433e536f52f4e259a69a073fd9c89fd
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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