N-methyl-2-pyrrolidone → (R)-tert-butyl 4-(4-chloropyrido[4,3-d]pyridazin-1-yl)-3-methylpiperazine-1-carboxylate

HRID 1514374

Reaktionsgleichung

[CH3:1][C@H:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.Cl[C:16]1[N:21]=[N:20][C:19]([Cl:22])=[C:18]2[CH:23]=[N:24][CH:25]=[CH:26][C:17]=12.CCN(C(C)C)C(C)C.CN1C(=O)CCC1>O>[Cl:22][C:19]1[C:18]2[CH:23]=[N:24][CH:25]=[CH:26][C:17]=2[C:16]([N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:3][C@H:2]2[CH3:1])=[N:21][N:20]=1

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

To (R)-tert-butyl 3-methylpiperazine-1-carboxylate (3.30 g, 16.5 mmol) and 1,4-dichloropyrido[4,3-d]pyridazine 3 (3.00 g, 15.0 mmol), suspended in Hünig's base (9.14 ml, 52.5 mmol) was added NMP (6 ml). The reaction was stirred at 100° C. The reaction contents were poured into water (120 mL) and extracted with dichloromethane (3×50 mL). Silica gel chromatography (gradient elution 20 to 80% EtOAc in hexanes) afforded 110 mg of (R)-tert-butyl 4-(4-chloropyrido[4,3-d]pyridazin-1-yl)-3-methylpiperazine-1-carboxylate 26 eluting after the 1-substitution product. 1H NMR (500 MHz, CDCl3) δ ppm 9.66 (s, 1H) 9.06 (d, J=6.1 Hz, 1H) 7.77 (d, J=5.5 Hz, 1H) 3.28-4.23 (m, 7H) 1.51 (s, 9H) 1.28 (d, J=6.7 Hz, 3H).

Aufarbeitung

customThe reaction contents
extractionextracted with dichloromethane (3×50 mL)
washSilica gel chromatography (gradient elution 20 to 80% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag: ord-2036677330884f19908074fb1d765c7e
Quelldatensatz: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08222251B2

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