Sodium hydride → HCID 67247661, compound

HRID 60287Notes

Reaction equation

HRID 60287 reaction equation
[CH3:1][C:2]1([CH2:8][OH:9])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[H-].[Na+].Cl[C:13]1[C:21]2[C:20]3[CH:22]=[C:23]([C:26]#[N:27])[N:24]=[CH:25][C:19]=3[N:18]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:17]=2[N:16]=[CH:15][CH:14]=1>O1CCOCC1.CN(C)C=O.O.C(OCC)(=O)C>[CH3:1][C:2]1([CH2:8][O:9][C:13]2[C:21]3[C:20]4[CH:22]=[C:23]([C:26]#[N:27])[N:24]=[CH:25][C:19]=4[N:18]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:17]=3[N:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 22507737(4-Methylpiperidin-4-yl)methanolHCID 582666684-Chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 67247661HCID 67247661, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (4-methylpiperidin-4-yl)methanol (989 mg, 7.7 mmol) in 1,4-dioxane (18 mL) and N,N-dimethylformamide (12 mL) was added sodium hydride as 60% dispersion in mineral oil (670 mg, 28 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 (428 mg, 1.2 mmol) was added in one portion and the reaction mixture was heated at 40° C. for 18 hours. The cooled reaction 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, 40 g, ISCO, 1-20% methanol in methylene chloride) to afford the title compound as an off-white solid, which was used in the next step without any further purification (300 mg, 56%).

Workup

  1. additionwas added in one portion
  2. customThe cooled reaction mixture
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified flash chromatography (silica, 40 g, ISCO, 1-20% methanol in methylene chloride)

Sources & evidence

ORD record
ord-9bfecbd624714c69ad6584e822cff6de
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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