Methyl Isocyanate → 4-(5,7-difluoro-3-methyl-4-(6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide

HRID 1618772Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1618772
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[CH:27]=3)[C:22]3([CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[N:7]2.[CH3:40][N:41]=[C:42]=[O:43]>C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)[CH:27]=3)[C:22]3([CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][N:16]([C:42]([NH:41][CH3:40])=[O:43])[CH2:15][CH2:14]1)=[N:7]2

Komponenten

4

Edukt 2

HCID 12228Methyl IsocyanateHCID 672844611'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Produkt 1

HCID 672858154-(5,7-difluoro-3-methyl-4-(6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1′-(5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinolin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (50 mg, 0.093 mmol) was dissolved in DCM (5.0 mL), and treated with methylisocyanate (5.50 μL, 0.093 mmol) and the reaction was stirred at rt for 2.5 h. After this time the reaction was concentrated to dryness and the residue was purified using an SCX column (compound loaded in MeOH and using 2M ammonia in MeOH as eluent) to give 4-(5,7-difluoro-3-methyl-4-(6′-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]-1′(2′H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide. 1H NMR (400 MHz, chloroform-d) δ ppm 7.55 (1H, d, J=2.3 Hz), 7.34 (1H, dt, J=9.8, 1.3 Hz), 6.75 (1H, ddd, J=11.8, 9.0, 2.4 Hz), 5.65 (1H, d, J=2.3 Hz), 4.69 (1H, q, J=4.2 Hz), 4.03-4.20 (2H, m), 3.80-3.97 (2H, m), 3.68-3.80 (4H, m), 3.48-3.67 (6H, m), 3.27-3.48 (4H, m), 2.90-3.04 (4H, m), 2.85 (3H, d, J=4.5 Hz), 2.19-2.39 (5H, m), 1.78 (1H, d, J=13.5 Hz), 1.69 (1H, d, J=13.5 Hz). Mass Spectrum (ESI) m/e=594.4 (M+1).

Aufarbeitung

  1. concentrationAfter this time the reaction was concentrated to dryness
  2. customthe residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-1d21d16e457a424ba577102439c92bfc
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765940B2

Notizen zur Reaktion

Wird geladen…