Water → HCID 86685991, compound

HRID 2277697Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:8]([C:10]2[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=2)[OH:9])[CH:5]=[N:6][CH:7]=1.[Cl:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[C:23](=[O:27])[NH:22][CH2:21][CH2:20]2.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1.[Cu]I>[Cl:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[C:23](=[O:27])[N:22]([C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]([C:10]3[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=3)=[O:9])[CH:3]=1)[CH2:21][CH2:20]2

Participants

Conditions

Temperature: 150 °C

Procedure

(5-Bromo-pyridin-3-yl)-(1-methyl-1H-imidazol-2-yl)-methanol (150 mg, 0.56 mmol), 6-chloro-3,4-dihydro-2H-isoquinolin-1-one (90 mg, 0.49 mmol) (intermediate A-2), CuI (30 mg, 0.16 mmol), Cs2CO3 (330 mg, 1.0 mmol) and (+)-(1S,1S)-1,2-diaminocyclohexane (0.08 mL, 0.64 mmol) were dissolved in dioxane (4.0 mL). The resulting mixture was heated at 150° C. for 2 hours before it was poured into H2O (50 mL) and extracted with EtOAc (2×75 mL). The organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give the title compound (4.5 mg, 2.5%) as light yellow oil. MS: 367.1 (M+H+).

Workup

extractionextracted with EtOAc (2×75 mL)
washThe organic layer was washed with brine
customdried over anhy
filtrationNa2SO4, filtered
concentrationconcentrated in vacuo
customto give a crude product which
customwas then purified by prep-HPLC

Sources & evidence

ORD record: ord-dfc93967d81c4b9a946ed7f0d86d8cf2
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133158B2

Reaction notes

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