Sodium hydride → HCID 58365107, compound

HRID 60292Notes

Reaction equation

HRID 60292 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([OH:8])[CH2:3]1.[H-].[Na+].Cl[C:12]1[C:20]2[C:19]3[CH:21]=[C:22]([C:25]#[N:26])[N:23]=[CH:24][C:18]=3[N:17]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:16]=2[N:15]=[CH:14][CH:13]=1>O1CCCC1.CN(C)C=O.O.C(OCC)(=O)C>[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([O:8][C:12]2[C:20]3[C:19]4[CH:21]=[C:22]([C:25]#[N:26])[N:23]=[CH:24][C:18]=4[N:17]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:16]=3[N:15]=[CH:14][CH:13]=2)[CH2:3]1

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 2759333(3R)-piperidin-3-ol hydrochlorideHCID 582666684-Chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 58365107HCID 58365107, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (R)-piperidin-3-ol hydrogen chloride (169 mg, 1.2 mmol) in tetrahydrofuran (4.5 mL) and N,N-dimethylformamide (1 mL) was added sodium hydride as 60% dispersion in mineral oil (200 mg, 5.0 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 (200 mg, 0.56 mmol) was added in one portion and the reaction mixture was stirred at this temperature for 10 minutes before being warmed to 40° C. for 4 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 a yellow solid, which was used in the next step without any further purification (236 mg, 100%).

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-4c16e7beb2db49128efe846ce6f537df
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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