Potassium Carbonate → N-(3-ethynylphenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy)quinazolin-4-amine

HRID 712407노트

반응식

HRID 712407 반응식
[O:1]1[CH:6]2[CH2:7][NH:8][CH2:9][CH:5]2[O:4][CH2:3][CH2:2]1.[C:10]([C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:29][CH2:30][CH2:31][CH2:32]Cl)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1)#[CH:11].C([O-])([O-])=O.[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[C:10]([C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:29][CH2:30][CH2:31][CH2:32][N:8]4[CH2:7][CH:6]5[O:1][CH2:2][CH2:3][O:4][CH:5]5[CH2:9]4)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1)#[CH:11]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 82418726hexahydro-2H-[1,4]dioxino[2,3-c]pyrroleHCID 867294706-(3-chloropropoxy)-N-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine

생성물 1

HCID 71573027N-(3-ethynylphenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy)quinazolin-4-amine수율 50%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

A mixture of hexahydro-2H-[1,4]dioxino[2,3-c]pyrrole (0.31 g, 2.40 mmol, 1.20 eq), N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (0.74 g, 2.00 mmol, 1.00 eq), anhydrous K2CO3 (1.00 g, 7.20 mmol, 3.60 eq) and tetrabutylammonium iodide (37 mg, 0.10 mmol, 0.05 eq) in DMF (8 mL) was heated at 70° C. for 11 h. The reaction mixture was cooled to room temperature and quenched with water (10 mL). The resulted mixture was diluted with EtOAc (20 mL) and the organic phase was separated from the mixture. The water phase was extracted with EtOAc (20 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH) to give the crude product, which was recrystallized from CH2Cl2/PE to afford the title compound as a pale yellow solid (0.46 g, 50.00%), HPLC: 96.10%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 461.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.98 (3H, s), 2.09 (2H, m), 2.73 (2H, m), 2.78 (2H, m), 2.97 (2H, dd, J=4.4, 10.4 Hz), 3.09 (1H, s), 3.55 (2H, m), 3.79 (2H, m), 3.99 (3H, s), 4.11 (2H, m), 4.22 (2H, t, J=6.8 Hz), 7.24 (2H, m), 7.25-7.28 (1H, m), 7.35 (1H, t, J=8.0 Hz), 7.67 (1H, br s), 7.80 (1H, m), 786 (1H, m) ppm.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water (10 mL)
  3. additionThe resulted mixture was diluted with EtOAc (20 mL)
  4. customthe organic phase was separated from the mixture
  5. extractionThe water phase was extracted with EtOAc (20 mL×3)
  6. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH)
  9. customto give the crude product, which
  10. customwas recrystallized from CH2Cl2/PE

출처 및 근거

ORD 기록
ord-e8717d0494f94908b0cf40aaa33b6144
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181277B2

반응 노트

불러오는 중…