Diisopropylethylamine → 1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)urea

HRID 631385Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 631385
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].C(N(CC)C(C)C)(C)C.[C:32]1([C:38]2[O:42][N:41]=[C:40]([NH:43][C:44](=O)[O:45]C3C=CC=CC=3)[CH:39]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([NH:19][C:44]([NH:43][C:40]2[CH:39]=[C:38]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[O:42][N:41]=2)=[O:45])[CH:20]=[CH:21][CH:22]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 59394374Phenyl 5-phenylisoxazol-3-ylcarbamate

Produkt 1

HCID 569538691-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)ureaAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (90 mg, 0.3 mmol), in tetrahydrofuran (1.5 mL) was treated with N,N-diisopropylethylamine (78 μl, 0.45 mmol), 4-(dimethylamino)pyridine (1.8 mg, 0.015 mmol) and phenyl 5-phenylisoxazol-3-ylcarbamate from the previous step (126 mg, 0.45 mmol). The reaction mixture was heated to 50° C. for 2.5 h. After cooling to room temperature, the mixture was partitioned between dichloromethane and a saturated solution of sodium bicarbonate. The water phase was back extracted three times with dichloromethane and the organics combined and dried (MgSO4). Concentration under reduced pressure gave a residue which was purified by preparative HPLC (phenylhexyl reverse phase column). The obtained solid was triturated with anhydrous diethyl ether to afford 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)urea as a white solid (47.16 mg, 32%). 1H NMR (300 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.08 (s, 1H), 8.58 (s, 1H), 7.86 (d, 2H), 7.87-7.51 (m, 4H), 7.51-7.40 (m, 2H), 7.31-7.21 (m, 3H), 7.00 (d, 1H), 4.00 (s, 6H); LC-MS (ESI) m/z 484 (M+H)+.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between dichloromethane
  3. extractionThe water phase was back extracted three times with dichloromethane
  4. dry with materialdried (MgSO4)
  5. concentrationConcentration under reduced pressure
  6. customgave a residue which
  7. customwas purified by preparative HPLC (phenylhexyl reverse phase column)
  8. customThe obtained solid was triturated with anhydrous diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-9aa4fb300ad748b6b05d0ba72932d87d
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09320739B2

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