Pyrazole → HCID 46207736, compound

HRID 334333Notes

Reaction equation

HRID 334333 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]=[CH: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.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)[C@@H]1CCCC[C@H]1N>CS(C)=O.[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]=[CH: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

7

Reactant 4

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 87374061HCID 87374061, compound

Product 1

HCID 46207736HCID 46207736, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of rac-6-[(6-chloropyridin-3-yl)methyl]-3-[trans-2-hydroxycyclohexyl]benzo[h]quinazolin-4(3H)-one (0.050 g, 0.12 mmol) and pyrazole (0.024 g, 0.36 mmol) in 2 mL of DMSO under an atmosphere of nitrogen was added cesium carbonate (0.24 mL, 1 N aqueous, 0.24 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (1.7 mg, 0.012 mmol), and copper(I) iodide (2.3 mg, 0.012 mmol). The mixture was heated at 130° C. for 24 h, cooled to rt, and purified via preparative reverse phase HPLC. The appropriate fractions were concentrated in vacuo. The residue was taken up in saturated aqueous sodium bicarbonate and extracted 3 times with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 452.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 9.01-8.99 (m, 1H), 8.50 (s, 1H), 8.32-8.30 (m, 2H), 8.02 (s, 1H), 7.93-7.91 (m, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.69-7.64 (m, 3H), 7.56 (d, J=8.4 Hz, 1H), 6.43 (s, 2H), 4.63 (br s, 1H), 4.09 (br s, 1H), 2.28-2.22 (m, 1H), 2.14-2.00 (m, 1H), 1.94-1.84 (m, 3H), 1.60-1.40 (m, 3H), 1.18-1.10 (m, 1H).

Workup

  1. temperaturecooled to rt
  2. custompurified via preparative reverse phase HPLC
  3. concentrationThe appropriate fractions were concentrated in vacuo
  4. extractionextracted 3 times with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-77a826eee91f4e568c4249c8c84d3e86
Source dataset
uspto-grants-2014_11
Patent number
US08883810B2

Reaction notes

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