Dimethylformamide → 2-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline

HRID 2092538

Reaktionsgleichung

Reaktionsgleichung von HRID 2092538
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:7][C:8]([Cl:12])=[N:9]2)=[CH:4][CH:3]=1.[CH3:19][C:20]1[O:24][C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>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>[Cl:12][C:8]1[N:7]=[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[C:10](=[CH:11][C:2]([C:23]3[O:24][C:20]([CH3:19])=[CH:21][CH:22]=3)=[CH:3][CH:4]=2)[N:9]=1

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27368814,4,5,5-Tetramethyl-2-(5-methylfuran-2-yl)-1,3,2-dioxaborolaneHCID 866657584-(7-Bromo-2-chloroquinazolin-4-yl)morpholine

Produkt 1

HCID 866657782-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazolineAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a 50 mL round bottom flask, 7-bromo-2-chloro-4-morpholin-4-yl-quinazoline (2 g, 0.0061 mol), 5-methyl-2-furanboronic acid pinacol ester (1.1 g, 0.0091 mol), sodium carbonate (0.969 g, 0.0092 mol), DMF (80 mL) and water (20 mL) were added and degassed the reaction vessel with nitrogen for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (0.213 g, 0.0003 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified; using column chromatography (60-120 silica gel, 0-20% ethyl acetate in hexane) to yield the desired product [1.4 g, 70%]. 1H NMR: (400 MHz, CDCl3): δ 8.01 (d, J=1.6 Hz, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.68 (dd, J′=8.8 Hz, J″=1.6 Hz, 1H), 6.78 (d, J=3.2, 1H), 6.14-6.45 (m, 1H), 3.88 (m, 8H), 2.42 (s, 3H); LC-MS (ESI): Calculated mass: 329.1; Observed mass: 330.0 [M+H]+ (RT: 1.71 min).

Aufarbeitung

  1. customdegassed the reaction vessel with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified

Quellen und Nachweise

ORD-Eintrag
ord-43b44de035bd4347ad38a454e6c44775
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440662B2

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