Dichloromethane → 2-(3-((4-((4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one

HRID 712527ノート

反応式

HRID 712527 の反応式
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH:8]2[CH2:10][CH2:11][O:12][C:13](=[O:14])[CH:7]2[CH2:6]1.C([O-])([O-])=O.[K+].[K+].[F:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([OH:39])[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[CH:24][CH:23]=1.C(Cl)Cl>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:21][C:22]1[CH:23]=[CH:24][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([O:39][CH2:2][CH2:3][CH2:4][N:5]4[CH2:9][CH:8]5[CH2:10][CH2:11][O:12][C:13](=[O:14])[CH:7]5[CH2:6]4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[CH:26][CH:27]=1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 867294684-((4-Fluorophenyl)amino)-7-methoxyquinazolin-6-olHCID 867294832-(3-chloropropyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one

生成物 1

HCID 867295252-(3-((4-((4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one収率 37.3%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

To a solution of 2-(3-chloropropyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one (0.25 g) in DMF (8 mL) was added K2CO3 (3.0 eq), 4-((4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.38 g) and tetrabutylammonium iodide (0.1 eq). The reaction mixture was heated to 90° C. and stirred for 10 h. To the mixture was added CH2Cl2 (100 mL). The mixture was washed with water and brine. The organic layer 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 product (0.20 g, 32.50%), HPLC: 97.35%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 467.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.06-2.12 (m, 4H), 2.35 (d, J=2.92 Hz, 1H), 2.51-2.58 (m, 3H), 2.76-2.79 (m, 2H), 2.97-3.02 (m, 1H), 3.49-3.50 (m, 1H), 3.52 (s, 1H), 4.00 (s, 3H), 4.18 (d, J=1.80 Hz, 1H), 4.21-4.24 (m, 1H), 4.35-4.40 (m, 1H), 7.13 (t, J=8.80 Hz, 1H), 7.24 (d, J=9.48 Hz, 1H), 7.41 (s, 1H), 7.68 (m, 2H), 7.95-7.98 (m, 1H), 8.28 (s, 1H), 8.63 (s, 1H) ppm.

後処理

  1. washThe mixture was washed with water and brine
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. 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-a51454ae5fc041f08858fe9fdfee4f30
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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