Pyrazole → HCID 53236426, compound

HRID 407182Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 1-[(5-bromopyridin-2-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-oxo-4H-quinolizine-3-carboxamide (Example 2, 0.045 g, 0.099 mmol) and pyrazole (0.020 g, 0.30 mmol) in 2 mL of DMSO under an atmosphere of nitrogen was added aqueous cesium carbonate (1 M, 0.20 mL, 0.20 mmol), trans-N, N-dimethylcyclohexane-1,2-diamine (0.014 g, 0.10 mmol), and copper(I) iodide (0.014 g, 0.076 mmol). The mixture was heated at 120° C. for 15 h, cooled to rt, and subjected to purification via reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 444.0 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 9.46 (d, J=7.6 Hz, 1H), 8.93 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.17-8.08 (m, 2H), 7.85-7.82 (m, 1H), 7.75 (s, 1H), 7.49-7.44 (m, 2H), 6.56-6.55 (m, 1H), 4.53 (s, 2H), 3.86-3.82 (m, 1H), 3.74-3.70 (m, 1H), 2.13-2.02 (m, 2H), 1.89-1.73 (m, 13H), 1.43-1.33 (m, 3H).

Workup

temperaturecooled to rt
customsubjected to purification via reverse phase HPLC

Sources & evidence

ORD record: ord-7982ed28ae7046959deb32f6edda99cd
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754220B2

Reaction notes

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