Dichloromethane → HCID 71573378、化合物

HRID 712445ノート

反応式

HRID 712445 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][CH2:39][O:40][CH2:41][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][CH2:39][O:40][CH2:41][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 86729488HCID 86729488、化合物

生成物 1

HCID 71573378HCID 71573378、化合物収率 44%

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 (60 mg) in DMF (6 mL) was added K2CO3 (66 mg) and tetrabutylammonium iodide (5 mg). The mixture was stirred for 10 min at room temperature, to this, a solution of 2-(3-chloropropyl)octahydropyrano[3,4-c]-pyrrole (38 mg) in DMF (1 mL) was added. The reaction mixture was heated at 90° C. for 12 h under N2 and CH2Cl2 (100 mL) was added. Then the mixture was washed with water followed by brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound (40 mg, 43.95%), HPLC: 98.50%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 488.0 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.26-1.29 (m, 2H), 1.37 (s, 3H), 2.33-2.37 (m, 3H), 2.59 (s, 1H), 3.03 (s, 1H), 3.44-3.47 (m, 1H), 3.50 (s, 1H), 3.72 (d, J=3.28 Hz, 1H), 3.78 (d, J=1.76 Hz, 1H), 3.81 (s, 1H), 3.87-3.89 (m, 1H), 3.99 (s, 3H), 4.50-4.55 (m, 2H), 7.11 (t, J=17.68 Hz, 1H), 7.25 (d, J=15.28 Hz, 1H), 7.35 (m, 1H), 7.82-7.86 (m, 1H), 8.13 (s, 1H), 8.22-8.25 (m, 1H), 8.63 (s, 1H), 8.92 (s, 1H) ppm.

後処理

  1. temperatureThe reaction mixture was heated at 90° C. for 12 h under N2
  2. washThen the mixture was washed with water
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated 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-52585191c18c4a358f11339ec69ad9c6
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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