Sodium hydride → HCID 86723753, compound

HRID 577526Notes

Reaction equation

[CH3:1][C:2]1[C:3]([O:13][CH:14]([CH3:16])[CH3:15])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].[CH2:19]([O:26][C:27]1[C:32]([CH2:33]Cl)=[C:31]([CH3:35])[CH:30]=[C:29]([CH3:36])[N:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH2:19]([O:26][C:27]1[C:32]([CH2:33][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([CH3:1])[C:3]([O:13][CH:14]([CH3:16])[CH3:15])=[CH:4][CH:5]=3)[C:10]2=[O:12])=[C:31]([CH3:35])[CH:30]=[C:29]([CH3:36])[N:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a 0° C. solution of 8-methyl-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (107a, 30 mg, 0.14 mmol) in tetrahydrofuran (0.46 mL) was added 60% sodium hydride (18 mg, 0.45 mmol). After 30 minutes 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 43 mg, 0.16 mmol) was added and the resulting mixture was heated at 50° C. for 16 hours. The reaction mixture was quenched with water (1 mL) then extracted with ethyl acetate (20 mL), washed with brine (2 mL), dried over sodium sulfate, filtered, then concentrated under vacuum. The residue was purified by column chromatography (EtOAc/heptanes, 0-100), to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-methyl-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (107b, 46 mg, 76%) as a colorless oil.

Workup

customThe reaction mixture was quenched with water (1 mL)
extractionthen extracted with ethyl acetate (20 mL)
washwashed with brine (2 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by column chromatography (EtOAc/heptanes, 0-100)

Sources & evidence

ORD record: ord-a0e3696a7a1e46269600e76f58ac9a9b
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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