1H-Pyrazol-3-amine, 5-methyl- → tert-butyl 4-[4-[5-cyano-3-methyl-6-(2,3,6-trifluorophenyl)-2,4-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl]phenyl]piperazine-1-carboxylate

HRID 336844Notes

Reaction equation

HRID 336844 reaction equation
O=[C:2]([C:6]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]([F:13])[C:7]=1[F:14])[CH2:3][C:4]#[N:5].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[CH:19][CH:18]=1)=O.[NH2:36][C:37]1[CH:41]=[C:40]([CH3:42])[NH:39][N:38]=1>C(#N)C>[C:4]([C:3]1[CH:15]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[C:41]2[C:40]([CH3:42])=[N:39][NH:38][C:37]=2[NH:36][C:2]=1[C:6]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]([F:13])[C:7]=1[F:14])#[N:5]

Participants

5

Reactant 3

HCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 2795509Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylateHCID 670737223-Oxo-3-(2,3,6-trifluorophenyl)propanenitrile

Product 1

HCID 178434166tert-butyl 4-[4-[5-cyano-3-methyl-6-(2,3,6-trifluorophenyl)-2,4-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl]phenyl]piperazine-1-carboxylateYield 81.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 1.1 g (5.52 mmol) of 3-oxo-3-(2,3,6-trifluorophenyl)propanenitrile diluted in 20 ml of acetonitrile are respectively added 1.60 g (5.52 mmol) of tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate and 0.53 g (5.52 mmol) of 3-amino-5-methyl-pyrazole. The reaction mixture is refluxed for 4 h then the solvent is concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 5:5) then the solid obtained is triturated in ethyl acetate and dried to yield 2.48 g (81%) of tert-butyl 4-(4-(5-cyano-3-methyl-6-(2,3,6-trifluorophenyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)piperazine-1-carboxylate in the form of a yellow solid.

Workup

  1. temperatureThe reaction mixture is refluxed for 4 h
  2. concentrationthe solvent is concentrated
  3. customThe residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 5:5)
  4. customthe solid obtained
  5. customis triturated in ethyl acetate
  6. customdried

Sources & evidence

ORD record
ord-a2fb4715e230448ab762b8154b88c250
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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