Trifluoroacetic acid → HCID 118093871, compound

HRID 1056951Notes

Reaction equation

HRID 1056951 reaction equation
[NH2:1][C:2]1[C:3]([O:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=2[F:36])=[C:4]([C:9]2[C:10]3[C:11](=[N:17][N:18](COCC[Si](C)(C)C)[CH:19]=3)[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[CH:37]([O-])([O-])OCC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.FC(F)(F)C(O)=O>O1CCCC1.C(Cl)Cl>[F:36][C:30]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:29]=1[O:28][C:3]1[C:2]2[N:1]=[CH:37][NH:8][C:7]=2[CH:6]=[CH:5][C:4]=1[C:9]1[C:10]2[CH:19]=[N:18][NH:17][C:11]=2[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 521998p-Toluenesulfonic acid monohydrateHCID 53630039EthylorthoformateHCID 123212492HCID 123212492, compound

Product 1

HCID 118093871HCID 118093871, compoundYield 60.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-[3,4-diamino-2-(2,4-difluorophenoxyl)phenyl]-6-methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (50.0 mg, 0.0973 mmol) in tetrahydrofuran (0.842 mL) was treated with ethyl orthoformate (48.6 μL, 0.292 mmol) followed by p-toluenesulfonic acid monohydrate (1.85 mg, 0.00973 mmol) and stirred at 50° C. for 1 h. The reaction mixture was diluted with methylene chloride (4.0 mL), treated with trifluoroacetic acid (4.0 mL), and heated at 40° C. for 2 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 (23 mg, 60%). 1H NMR (500 MHz, DMSO-d6) δ 14.02 (s, 1H), 12.79 (br s, 1H), 8.22 (s, 1H), 7.72 (s, 1H), 7.56 (d, J=8.2 Hz, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.30-7.14 (m, 2H), 6.73 (dd, J=8.0, 8.0 Hz, 1H), 6.66-6.49 (m, 1H), 3.52 (s, 3H); LCMS calculated for C20H14F2N5O2 (M+H)+: m/z=394.1. found: 394.1.

Workup

  1. temperatureheated at 40° C. for 2 h
  2. customThe reaction mixture was purified via preparative LCMS (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-1bdb0b5862cd42bd896613d1df8bf920
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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