Pyrazole → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}pyrido[2,3-h]quinazolin-4(3H)-one

HRID 1183825Notes

Reaction equation

HRID 1183825 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[N:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.[NH:31]1[CH:35]=[CH:34][CH:33]=[N:32]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>CS(C)=O.O.ClCCl.[Cu]I>[OH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]1[N:13]1[C:12](=[O:30])[C:11]2[C:16](=[C:17]3[CH:22]=[CH:21][CH:20]=[N:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

Participants

9

Reactant 4

HCID 1048PyrazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 532607706-[(6-Chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[2,3-h]quinazolin-4(3H)-one

Product 1

HCID 532612333-[(1S,2S)-2-Hydroxycyclohexyl]-6-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}pyrido[2,3-h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[2,3-h]quinazolin-4(3H)-one (0.063 g, 0.15 mmol) and pyrazole (0.015 g, 0.22 mmol) in 1 mL of DMSO and 0.2 mL of water under an atmosphere of nitrogen was added potassium phosphate (0.095 g, 0.45 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (21.3 mg, 0.150 mmol), and copper(I) iodide (8.6 mg, 0.045 mmol). The mixture was heated at 120° C. for 30 h, cooled to rt, and diluted with dichloromethane. The organic solution was washed 3× with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 453.2034 for [M+H]+ [Calc'd for C26H25N6O2, [M+H]+=453.2034]: 1H NMR (400 MHz, CDCl3) δ 9.24-9.22 (m, 1H), 9.10-9.08 (m, 1H), 8.50 (s, 1H), 8.46 (s, 1H), 8.27-8.26 (m, 2H), 7.85-7.77 (m, 2H), 7.68 (s, 1H), 7.62-7.59 (m, 1H), 6.42 (s, 1H), 4.68 (s, 2H), 4.66-4.64 (m, 1H), 4.02 (br s, 1H), 2.27-2.25 (m, 1H), 2.06-2.03 (m, 1H), 1.90 (br s, 3H), 1.56-1.44 (m, 3H).

Workup

  1. temperaturecooled to rt
  2. washThe organic solution was washed 3× with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel chromatography
  7. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-648156417c4a4c128e476be894ef29ba
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

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