Diisopropylethylamine → N,3-dimethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide

HRID 44325

Reaktionsgleichung

Reaktionsgleichung von HRID 44325
O[CH2:2][C:3]1[CH:16]=[N:15][C:6]2[C:7]3[N:8]([CH:12]=[CH:13][CH:14]=3)[C:9](=[O:11])[NH:10][C:5]=2[CH:4]=1.Cl.Cl.[CH3:19][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)=[C:24]([CH3:34])[CH:23]=1.[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[CH3:19][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:16]=[N:15][C:6]4[C:7]5[N:8]([CH:12]=[CH:13][CH:14]=5)[C:9](=[O:11])[NH:10][C:5]=4[CH:4]=3)[CH2:30][CH2:29]2)=[C:24]([CH3:34])[CH:23]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 509163263-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-oneHCID 66775618N,3-dimethyl-4-(piperazin-1-yl)benzamide dihydrochloride

Produkt 1

HCID 50916507N,3-dimethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamideAusbeute 39,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 7854PropionitrileLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a suspension of 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (75.00 mg, 0.348 mmol), N,3-dimethyl-4-(piperazin-1-yl)benzamide dihydrochloride (133 mg, 0.436 mmol) and (cyanomethyl)trimethylphosphonium iodide (136 mg, 0.558 mmol) in Propiononitrile (Volume: 2.00 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.425 mL, 2.439 mmol) at 23° C. The reaction was stirred at 95° C. for 15 hr. The suspension was cooled to 23° C., concentrated via rotary evaporation, re-constituted in ACN (2.0 mL), stirred for 15 min, filtered, rinsed with ACN (3×1 mL) and dried in vacuo. The crude solid was re-suspended in ACN (2.0 mL), heated to reflux, cooled to 23° C., filtered, rinsed with ACN (3×2.0 mL) to provide N,3-dimethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.0594 g, 0.138 mmol, 39.6% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.26 (s, 3 H) 2.53-2.66 (m, 4 H) 2.75 (d, J=4.55 Hz, 3 H) 2.86-2.96 (m, 4 H) 3.64 (s, 2 H) 6.71-6.76 (m, 1 H) 7.03 (d, J=8.34 Hz, 1 H) 7.07 (dd, J=3.66, 1.64 Hz, 1H) 7.58 (d, J=1.77 Hz, 1 H) 7.59-7.66 (m, 2 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.19 (q, J=4.29 Hz, 1 H) 8.36 (d, J=1.52 Hz, 1 H) 11.58 (s, 1 H). ESI-MS: m/z 431.4 (M+H)+. mp=264.0-266.3° C.

Aufarbeitung

  1. temperatureThe suspension was cooled to 23° C.
  2. concentrationconcentrated via rotary evaporation, re-constituted in ACN (2.0 mL)
  3. stirringstirred for 15 min
  4. filtrationfiltered
  5. washrinsed with ACN (3×1 mL)
  6. customdried in vacuo
  7. temperatureheated
  8. temperatureto reflux
  9. temperaturecooled to 23° C.
  10. filtrationfiltered
  11. washrinsed with ACN (3×2.0 mL)

Quellen und Nachweise

ORD-Eintrag
ord-9878b0a31e6b4a3cad5641962b203fbe
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541417B2

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