Dichloromethane → N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl) propoxy)quinazolin-4-amine

HRID 712440노트

반응식

HRID 712440 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].Cl[CH2:30][CH2:31][CH2:32][N:33]1[CH2:37][CH:36]2[CH2:38][O:39][CH2:40][CH:35]2[CH2:34]1.C(Cl)Cl>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:30][CH2:31][CH2:32][N:33]4[CH2:37][CH:36]5[CH2:38][O:39][CH2:40][CH:35]5[CH2:34]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 867294855-(3-chloropropyl)hexahydro-1H-furo[3,4-c]pyrrole

생성물 1

HCID 71573377N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl) propoxy)quinazolin-4-amine수율 64%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매2회

실험 절차

To a solution of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.19 g) in DMF (6 mL) was added K2CO3 (0.42 g) and tetrabutylammonium iodide (20 mg). The mixture was stirred at room temperature for 10 min, to this, a solution of 5-(3-chloropropyl)hexahydro-1H-furo[3,4-c]pyrrole (0.13 g) in DMF (2 mL) was added. The reaction mixture was heated at 80° C. for 14 h under N2 and treated with CH2Cl2 (100 mL), then washed with water and brine. The mixture was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound (180 mg, 60.04%), HPLC: 95.78%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 474.0 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.12 (t, J=13.28 Hz, 2H), 2.54 (s, 2H), 2.72 (t, J=13.32 Hz, 2H), 2.83 (d, J=9.00 Hz, 2H), 2.90 (s, 2H), 3.73 (t, J=5.36 Hz, 3H), 3.99 (s, 3H), 4.28 (t, J=13.24 Hz, 2H), 7.15 (t, J=17.60 Hz, 1H), 7.25 (d, J=7.32 Hz, 1H), 7.44 (s, 1H), 7.60-7.64 (m, 1H), 7.93-7.96 (m, 1H), 7.99 (s, 1H), 8.64 (s, 1H) ppm.

후처리

  1. temperatureThe reaction mixture was heated at 80° C. for 14 h under N2
  2. washwashed with water and brine
  3. dry with materialThe mixture was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

출처 및 근거

ORD 기록
ord-83de88d33aab402f969eaa1a34f00948
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181277B2

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