Sodium hydride → 4-((4-ethyl-1-methylpiperidin-4-yl)methoxy)-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60297Notes

Reaction equation

[CH2:1]([C:3]1([CH2:10][OH:11])[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1)[CH3:2].[H-].[Na+].Cl[C:15]1[C:23]2[C:22]3[CH:24]=[C:25]([C:28]#[N:29])[N:26]=[CH:27][C:21]=3[N:20](COCC[Si](C)(C)C)[C:19]=2[N:18]=[CH:17][CH:16]=1>O1CCCC1.O.C(OCC)(=O)C>[CH2:1]([C:3]1([CH2:10][O:11][C:15]2[C:23]3[C:22]4[CH:24]=[C:25]([C:28]#[N:29])[N:26]=[CH:27][C:21]=4[NH:20][C:19]=3[N:18]=[CH:17][CH:16]=2)[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1)[CH3:2]

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of (4-ethyl-1-methylpiperidin-4-yl)methanol (223 mg, 1.4 mmol) in tetrahydrofuran (3.2 mL) was added sodium hydride as 60% dispersion in mineral oil (57 mg, 1.4 mmol). The reaction mixture was stirred at ambient temperature for 5 minutes before 4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (150 mg, 0.42 mmol) was added in one portion and the reaction mixture was stirred at this temperature for 10 minutes, and then heated at 40° C. for 4 hours. The mixture was diluted with water (20 mL) and ethyl acetate (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 4 g, ISCO, 0-10% methanol in methylene chloride) to afford the title compound as a white foam, which was used in the next step without any further purification (152 mg, 76%).

Workup

additionwas added in one portion
customThe organic layer was separated
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
custompurified flash chromatography (silica, 4 g, ISCO, 0-10% methanol in methylene chloride)

Sources & evidence

ORD record: ord-8d9a85c2eefe40389a7517f27383710a
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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