1H-Pyrazol-3-amine, 5-methyl- → methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate

HRID 473211Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 473211
Br[C:2]1[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]([F:25])([F:24])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=2)[N:3]=1.[CH3:26][C:27]1[NH:31][N:30]=[C:29]([NH2:32])[CH:28]=1>O1CCOCC1>[F:24][C:16]([F:25])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:4]1[N:3]=[C:2]([NH:32][C:29]2[CH:28]=[C:27]([CH3:26])[NH:31][N:30]=2)[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=1

Komponenten

4

Edukt 2

HCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 86662705Methyl 4-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline-8-carboxylate

Produkt 1

HCID 56848866methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of methyl 4-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline-8-carboxylate (27 g, 65.5 mmol) in dioxane (300 mL) was added 5-methyl-1H-pyrazol-3-amine (12.7 g, 131 mmol) and the mixture was stirred at 50° C. overnight. The mixture was concentrated and the residue was triturated with water (1 L). The solid was collected by filtration, washed with water, and dried in air to afford methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate as a solid. (26.7 g, 95%). LC-MS (ESI) m/z 429.6 (M+H+). 1H NMR (500 MHz, DMSO-d6) δ 12.23 (1H, s), 10.86 (1H, s), 8.82 (1H, d, J=8.2 Hz), 8.67 (1H, d, J=2.6 Hz), 7.99 (3H, m), 7.68 (1H, t, J=8.0 Hz), 6.05 (1H, s), 3.83 (3H, s), 2.19 (3H, s).

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. customthe residue was triturated with water (1 L)
  3. filtrationThe solid was collected by filtration
  4. washwashed with water
  5. customdried in air

Quellen und Nachweise

ORD-Eintrag
ord-bf6be38a749145e1865d7e34c365c8ba
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633207B2

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