Sodium hydride → (R)-4-(piperidin-2-ylmethoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60301Notes

Reaction equation

HRID 60301 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[CH2:8][OH:9].[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>O1CCCC1.O.C(OCC)(=O)C>[NH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[CH2:8][O:9][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

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 582666684-Chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileHCID 67247105(r)-Piperidin-2-ylmethanol hydrochloride

Product 1

HCID 58365030(R)-4-(piperidin-2-ylmethoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (R)-piperidin-2-ylmethanol hydrogen chloride (510 mg, 3.4 mmol) in tetrahydrofuran (12 mL) was added sodium hydride as 60% dispersion in mineral oil (270 mg, 6.8 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 (550 mg, 1.5 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 5 hours. The cooled 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 a white solid, which was used in the next step without any further purification (470 mg, 70%).

Workup

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

Sources & evidence

ORD record
ord-5410fb997344478b97eeb8587f438720
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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