Pyrazole → HCID 86682405, compound

HRID 2365258Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (±)-5-[(6-chloropyridin-3-yl)methyl]-2-[trans-2-hydroxycyclohexyl]-1,2-dihydro-3H-pyrrolo[3,4-c]isoquinoline-3-one (Example 16, 0.040 g, 0.098 mmol) and pyrazole (0.020 g, 0.29 mmol) in 1 mL of dimethylsulfoxide under an atmosphere of nitrogen was added cesium carbonate (1.0 M aqeuous, 0.20 mL, 0.20 mmol), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (1.4 mg, 0.0098 mmol), and copper(I) iodide (0.93 mg, 0.0049 mmol). The mixture was heated at 120° C. for 15 hr, cooled to ambient temperature, and purified via preparative reverse phase HPLC to provide the titled compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 440.9 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 8.51-8.46 (m, 3H), 8.14 (d, J=8.2 Hz, 1H), 7.94-7.80 (m, 5H), 6.54-6.44 (m, 1H), 4.90 (s, 2H), 4.12-4.08 (m, 1H), 3.93-3.86 (m, 1H), 3.49-3.40 (m, 1H), 3.31 (s, 2H), 2.20-2.02 (m, 1H), 1.95-1.90 (m, 1H), 1.89-1.70 (m, 3H), 1.54-1.43 (m, 3H) ppm.

Workup

temperaturecooled to ambient temperature
custompurified via preparative reverse phase HPLC

Sources & evidence

ORD record: ord-2b2a45a1513f4ebeb45fe8e62da7f913
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697690B2

Reaction notes

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