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

HRID 60301Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 60301
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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5410fb997344478b97eeb8587f438720
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440976B2

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