Water → 4-[4-(Cyclopropylmethoxy)-1-methyl-1H-indazol-5-yl]-6-methyl-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 1056987Notes

Reaction equation

HRID 1056987 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([CH2:11][O:12][C:13]2[C:21]([C:22]3[C:23]4[CH:32]=[N:31][N:30](COCC[Si](C)(C)C)[C:24]=4[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=3)=[CH:20][CH:19]=[C:18]3[C:14]=2[CH:15]=[N:16][N:17]3[CH3:41])[CH2:10][CH2:9]1.[OH-].[NH4+].O>C(Cl)Cl.CO>[CH:8]1([CH2:11][O:12][C:13]2[C:21]([C:22]3[C:23]4[CH:32]=[N:31][NH:30][C:24]=4[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=3)=[CH:20][CH:19]=[C:18]3[C:14]=2[CH:15]=[N:16][N:17]3[CH3:41])[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 1238389734-(4-(cyclopropylmethoxy)-1-methyl-1H-indazol-5-yl)-6-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-7(6H)-one

Product 1

HCID 1180939404-[4-(Cyclopropylmethoxy)-1-methyl-1H-indazol-5-yl]-6-methyl-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-oneYield 67.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.564 mL) was added dropwise to a solution of 4-[4-(cyclopropylmethoxy)-1-methyl-1H-indazol-5-yl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.0549 g, 0.114 mmol) in methylene chloride (0.564 mL) and the resultant reaction mixture was stirred at RT for 30 min. The reaction mixture was concentrated in vacuo to yield a crude residue. The crude residue was dissolved in methanol (1.00 mL), followed by dropwise addition of 15.0 M solution of ammonium hydroxide in water (0.250 mL, 3.76 mmol). The resultant reaction mixture was stirred at RT for 30 min. 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 (26.8 mg, 67%). 1H NMR (500 MHz, DMSO-d6) δ 14.00 (br s, 1H), 8.23 (s, 1H), 7.72 (s, 1H), 7.38 (d, J=8.5 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.28 (s, 1H), 4.05 (d, J=6.8 Hz, 2H), 4.03 (s, 3H), 3.58 (s, 3H), 1.23-0.81 (m, 1H), 0.51-0.26 (m, 2H), 0.25-0.01 (m, 2H); LCMS calculated for C19H20N5O2 (M+H)+: m/z=350.2. found: 350.1.

Workup

  1. customthe resultant reaction mixture
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto yield a crude residue
  4. customThe resultant reaction mixture
  5. stirringwas stirred at RT for 30 min
  6. customThe reaction mixture was purified via preparative LCMS (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-3b1c8ff346bf4480a685d1bcb9f0d23a
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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