Sodium Carbonate → N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

HRID 1431602Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1431602
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[N:26][CH:27]=1)=[C:5]([CH3:20])[C:6]([C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=1)=[N:7]2.[NH2:31][C:32]1[N:37]=[C:36](Cl)[CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[NH2:31][C:32]1[N:37]=[C:36]([C:24]2[CH:23]=[C:22]([NH:21][C:4]3[C:3]4[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=4[F:1])[N:7]=[C:6]([C:13]4[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=4)[C:5]=3[CH3:20])[CH:27]=[N:26][CH:25]=2)[CH:35]=[CH:34][N:33]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2233322-Amino-4-chloropyrimidineHCID 596313385-(5,7-Difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid

Produkt 1

HCID 50907185N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A screw-cap vial was charged with 5-(5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid (200 mg, 0.49 mmol), 2-amino-4-chloropyrimidine (63.8 mg, 0.49 mmol), bis(triphenylphosphine)palladium (II) chloride (34.6 mg, 0.049 mmol), sodium carbonate (157 mg, 1.48 mmol), 1,4-dioxane (4 mL), and water (1 mL). The solution was stirred at 95° C. for 30 min, and then cooled to rt. The product was extracted with EtOAc and DCM, and the combined organic layer was dried over magnesium sulfate and cond. The crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM, then recrystallized in MeOH to afford N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=456.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (1H, s), 8.63 (1H, d, J=1.8 Hz), 8.56 (1H, d), 8.31 (1H, d, J=5.3 Hz), 8.13 (1H, d), 7.75 (1H, s), 7.70 (1H, m), 7.60 (1H, m), 7.49 (1H, m), 7.35 (1H, m), 7.09 (1H, s), 6.68 (2H, s), 2.45 (3H, s), 2.20 (3H, s).

Aufarbeitung

  1. temperaturecooled to rt
  2. extractionThe product was extracted with EtOAc and DCM
  3. dry with materialthe combined organic layer was dried over magnesium sulfate and cond
  4. customThe crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM
  5. customrecrystallized in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-d8fd525791f841c58f2b2477bc4d190f
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940724B2

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