Toluene → N-(4-(3-(4-(7-(5-methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)ureido)phenyl)acetamide

HRID 517479

Reaktionsgleichung

Reaktionsgleichung von HRID 517479
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([C:18]3[O:19][C:20]([CH3:23])=[CH:21][CH:22]=3)=[CH:7][CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:51])[NH:40][C:41]3[CH:46]=[CH:45][C:44]([NH:47][C:48](=[O:50])[CH3:49])=[CH:43][CH:42]=3)=[CH:34][CH:33]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>O.CCO>[CH3:23][C:20]1[O:19][C:18]([C:6]2[CH:5]=[C:4]3[C:9]([C:10]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:11][C:2]([C:32]4[CH:33]=[CH:34][C:35]([NH:38][C:39](=[O:51])[NH:40][C:41]5[CH:42]=[CH:43][C:44]([NH:47][C:48](=[O:50])[CH3:49])=[CH:45][CH:46]=5)=[CH:36][CH:37]=4)=[N:3]3)=[CH:8][CH:7]=2)=[CH:22][CH:21]=1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 67516983N-(4-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)phenyl)acetamideHCID 866657782-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline

Produkt 1

HCID 57335185N-(4-(3-(4-(7-(5-methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)ureido)phenyl)acetamideAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a 50 mL round bottom flask, 2-chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline (0.15 g, 0.00045 mol; prepared as described in Example 2; Scheme 6B), N-(4-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)phenyl)acetamide (0.23 g, 0.00059 mol; prepared according to the methods described in Scheme 9), cesium carbonate (0.44 g, 0.00135 mol), toluene (10 mL), EtOH (4 mL) and water (2 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd (PPh3)2Cl2 (0.022 g, 0.0000315 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 3 h. The reaction mixture was cooled to room temperature to get the precipitate. The precipitate was collected by filtration to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 3% MeOH in chloroform). The compound was further purified by flash column chromatography using 230-400 silica gel and 1.5% MeOH in chloroform to yield the title compound [0.0252 g, 10%]. 1H NMR (400 MHz, DMSO-d6): δ 9.86 (s, 1H), 8.92 (s, 1H), 8.67 (s, 1H), 8.42 (d, J=8.8 Hz, 2H), 8.01 (d, J=8.8 Hz, 2H), 7.74 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.39 (d, J=8.8 Hz, 2H), 7.17 (d, J=3.2 Hz, 1H), 6.32 (d, J=2.8 Hz, 1H), 3.83 (s, 4H), 3.80 (s, 4H), 2.41 (s, 3H), 2.02 (s, 3H). LC-MS (ESI): Calculated mass: 562.2; Observed mass: 563.1 (RT: 0.64 min).

Aufarbeitung

  1. customprepared
  2. additionwere added
  3. customThe reaction mixture was degassed with nitrogen for 5-10 min
  4. customagain degassed with nitrogen for 5-10 min
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customto get the precipitate
  7. filtrationThe precipitate was collected by filtration
  8. customto afford the crude product
  9. customThe crude product was purified
  10. customThe compound was further purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-be03e760063a49a58cc0b016dbd6a9fb
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115092B2

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