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 712440ノート

反応式

HRID 712440 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-83de88d33aab402f969eaa1a34f00948
出典データセット
uspto-grants-2015_11
特許番号
US09181277B2

反応ノート

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