Toluene → 1-(4-(7-(5-Methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)-3-(4-(2-oxopyrrolidin-1-yl)phenyl)urea

HRID 517480

반응식

HRID 517480 반응식
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.[O:24]=[C:25]1[CH2:29][CH2:28][CH2:27][N:26]1[C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]([NH:39][C:40]2[CH:45]=[CH:44][C:43](B3OC(C)(C)C(C)(C)O3)=[CH:42][CH:41]=2)=[O:38])=[CH:32][CH:31]=1.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:43]4[CH:44]=[CH:45][C:40]([NH:39][C:37]([NH:36][C:33]5[CH:34]=[CH:35][C:30]([N:26]6[CH2:27][CH2:28][CH2:29][C:25]6=[O:24])=[CH:31][CH:32]=5)=[O:38])=[CH:41][CH:42]=4)=[N:3]3)=[CH:8][CH:7]=2)=[CH:22][CH:21]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 675173641-(4-(2-Oxopyrrolidin-1-yl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 866657782-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline

생성물 1

HCID 675143031-(4-(7-(5-Methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)-3-(4-(2-oxopyrrolidin-1-yl)phenyl)urea수율 7%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
95 °C

실험 절차

To a 50 mL round bottom flask, 2-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline (0.12 g, 0.00036 mol; prepared as described in Example 2; Scheme 6B), 1-(4-(2-oxopyrrolidin-1-yl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.184 g, 0.00043 mol; prepared according to the methods described in Scheme 9), cesium carbonate (0.296 g, 0.0009 mol), toluene (7 mL), EtOH (7 mL) and water (3 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd (PPh3)2Cl2 (0.0128 g, 0.000018 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 and diluted with chloroform. The organic layer was separated, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified by flash column chromatography using 230-400 silica gel, 2% MeOH in chloroform. The compound was further purified by prep TLC using 4% MeOH in chloroform to yield the title compound [0.015 g, 7%]. 1H NMR (300 MHz, DMSO-d6): δ 8.92 (s, 1H), 8.75 (s, 1H), 8.43 (d, J=7.2 Hz, 2H), 8.02 (d, J=8.1 Hz, 2H), 7.75 (d, J=8.4 Hz, 1H), 7.62 (t, J=8.7 Hz, 4H), 7.48 (d, J=9 Hz, 2H), 7.17 (d, J=3.3 Hz, 1H), 6.32 (d, J=2.4 Hz, 1H), 3.83 (m, 10H), 2.47 (d, J=8.4 Hz, 2H), 2.41 (s, 3H), 2.08 (m, 2H); LC-MS (ESI): Calculated mass: 588.2; Observed mass: 589.2 (RT: 0.13 min).

후처리

  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
  6. additiondiluted with chloroform
  7. customThe organic layer was separated
  8. washwashed with water, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customto afford the crude product
  12. customThe crude product was purified by flash column chromatography
  13. customThe compound was further purified by prep TLC

출처 및 근거

ORD 기록
ord-a81d3bd6d8774afda17ae31ca0500efa
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115092B2

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