Diisopropylethylamine → HCID 46864646, Verbindung

HRID 69723Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69723
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.Cl.[CH2:18]([NH:20][C:21](=[O:35])[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][C:23]=1[F:34])[CH3:19].[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC>[CH2:18]([NH:20][C:21](=[O:35])[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([CH2:2][C:3]3[CH:12]=[N:11][C:10]4[N:9]5[CH2:13][CH2:14][CH2:15][C@H:8]5[C:7](=[O:16])[NH:6][C:5]=4[CH:4]=3)[CH2:30][CH2:29]2)=[CH:24][C:23]=1[F:34])[CH3:19]

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 66774972N-ethyl-2-fluoro-4-(piperazin-1-yl)benzamide hydrochloride

Produkt 1

HCID 46864646HCID 46864646, VerbindungAusbeute 18,12 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 7854PropionitrileLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (76 mg, 0.348 mmol), N-ethyl-2-fluoro-4-(piperazin-1-yl)benzamide hydrochloride (100 mg, 0.348 mmol), (cyanomethyl)trimethylphosphonium iodide (127 mg, 0.521 mmol) and N,N-diisopropylethylamine (0.303 ml, 1.738 mmol) were suspended in propiononitrile (Volume: 1.370 ml) and heated in a closed vial at 120° C. for 3 h. The reaction mixture became a dark brown suspension. 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-methanol (5:1, 6 mL) and dried in vacuum to afford (S)—N-ethyl-2-fluoro-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)benzamide (28.5 mg, 0.063 mmol, 18.12% yield) as a brownish solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13 (t, J=7.20 Hz, 3 H) 1.83-2.02 (m, 3 H) 2.18 (dd, J=6.44, 4.17 Hz, 1 H) 2.44-2.49 (m, 4 H) 2.81-3.01 (m, 4 H) 3.23-3.32 (m, 2 H) 3.34-3.44 (m, 3 H) 3.52-3.64 (m, 1 H) 3.93-4.01 (m, 1 H) 6.91 (td, J=8.21, 2.53 Hz, 1 H) 6.97 (d, J=1.77 Hz, 1 H) 7.00 (dd, J=11.37, 2.53 Hz, 1 H) 7.62 (d, J=1.52 Hz, 1 H) 7.67 (dd, J=8.46, 7.20 Hz, 1 H) 8.86 (t, J=5.43 Hz, 1 H) 10.45 (s, 1 H). [M+H] calc'd for C24H29FN6O2, 453; found, 453.

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-methanol (5:1, 6 mL)
  7. customdried in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-1b49c88cf79d4251911831928e3baed9
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822470B2

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