Diisopropylethylamine → (S)-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile

HRID 2097931Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2097931
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][C@H:8]3[C:7](=[O:16])[NH:6][C:5]=2[CH:4]=1.[CH3:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:21]#[N:22].[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC>[CH3:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:27][CH2:28][N:29]([CH2:2][C:3]2[CH:12]=[N:11][C:10]3[N:9]4[CH2:13][CH2:14][CH2:15][C@H:8]4[C:7](=[O:16])[NH:6][C:5]=3[CH:4]=2)[CH2:30][CH2:31]1)[C:21]#[N:22]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-oneHCID 600511423-Methyl-4-(piperazin-1-yl)benzonitrile

Produkt 1

HCID 46864685(S)-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrileAusbeute 49,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 7854PropionitrileLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (100 mg, 0.456 mmol), 3-methyl-4-(piperazin-1-yl)benzonitrile (92 mg, 0.456 mmol), (cyanomethyl)trimethylphosphonium iodide (166 mg, 0.684 mmol) and N,N-diisopropylethylamine (0.398 ml, 2.281 mmol) were suspended in propiononitrile (Volume: 1.370 ml) and heated in a closed vial at 90-120° C. for 4 h. The reaction mixture became a dark brown solution. It was cooled to room temperature, concentrated in vacuo, dissolved in DMSO (2 mL) and purified using HPLC (basic, 10-95% ACN in water). The fractions were concentrated in vacuo and the resulting solid was recrystallized from water (6 mL) and dried in vacuum to afford (S)-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile (90.1 mg, 0.224 mmol, 49.1% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.85-2.01 (m, 3 H) 2.12-2.21 (m, 1 H) 2.24 (s, 3 H) 2.43-2.55 (m, 4 H) 2.85-2.97 (m, 4 H) 3.35-3.44 (m, 3 H) 3.53-3.63 (m, 1 H) 3.95-4.03 (m, 1 H) 6.98 (d, J=2.02 Hz, 1 H) 7.05-7.12 (m, 1 H) 7.54-7.60 (m, 2 H) 7.62 (d, J=1.77 Hz, 1 H) 10.44 (s, 1 H). [M+H] calc'd for C23H26N6O, 403; found, 403.

Aufarbeitung

  1. temperatureIt was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. dissolutiondissolved in DMSO (2 mL)
  4. custompurified
  5. concentrationThe fractions were concentrated in vacuo
  6. customthe resulting solid was recrystallized from water (6 mL)
  7. customdried in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3d4afe71e9c4480698c8e8f6749d97ab
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08450323B2

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