Sodium Carbonate → N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

HRID 1431307Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1431307
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[N:25][C:26]=1[N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)=[C:5]([CH3:19])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:7]2.Cl[C:37]1[CH:42]=[C:41]([CH3:43])[N:40]=[C:39]([NH2:44])[N:38]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:44][C:39]1[N:38]=[C:37]([C:23]2[CH:22]=[C:21]([NH:20][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]=[CH:17][CH:16]=[CH:15][N:14]=4)[C:5]=3[CH3:19])[C:26]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[N:25][CH:24]=2)[CH:42]=[C:41]([CH3:43])[N:40]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 312751,4-DioxaneHCID 596311135-(5,7-Difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid

Produkt 1

HCID 59631544N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A solution of 5-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid (0.026 mmol, described herein), 4-chloro-6-methylpyrimidin-2-amine (3.7 mg, 0.026 mmol), sodium carbonate (8.18 mg, 0.077 mmol), dichlorobis(triphenylphosphine)palladium(ii) (1.8 mg, 2.57 μmol), 1,4-dioxane (560 μL) and water (140 μL) heated in a microwave at 120° C. for 60 min. The reaction was then cooled to rt and partitioned between EtOAc and water. The organic layer was dried (magnesium sulfate) and concentrated, and chromatography afforded N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.72-8.81 (1H, m), 8.52-8.61 (1H, m), 7.85-7.96 (2H, m), 7.61-7.71 (1H, m), 7.52-7.61 (1H, m), 7.47-7.52 (1H, m), 7.41 (1H, m), 7.03 (1H, m), 6.84-6.93 (1H, m), 5.22 (2H, br. s.), 3.94 (4H, br. s.), 3.45-3.73 (2H, m), 3.00-3.40 (2H, br. s.), 2.33-2.52 (3H, m), 2.15-2.29 (3H, m). Mass Spectrum (ESI) m/e=541.0 (M+1).

Aufarbeitung

  1. temperatureThe reaction was then cooled to rt
  2. custompartitioned between EtOAc and water
  3. dry with materialThe organic layer was dried (magnesium sulfate)
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-289d49ae7f6e49ca873e85607b080bf6
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940724B2

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