Hydrochloric Acid → Gefitinib

HRID 1803016ノート

反応式

HRID 1803016 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]3Cl)[CH2:3][CH2:2]1.[F:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=1[Cl:32].Cl>CO>[Cl:32][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:25]=1[F:24])[NH:29][C:14]1[C:13]2[C:18](=[CH:19][C:20]([O:21][CH3:22])=[C:11]([O:10][CH2:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)[N:17]=[CH:16][N:15]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 97083-Chloro-4-fluoroanilineHCID 226492214-Chloro-7-methoxy-6-(3-(4-morpholinyl)propoxy)quinazoline

生成物 1

HCID 123631Gefitinib収率 70%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
17.5 °C

実験手順

Methanol (1200 ml) and 6-(3-morpholino propoxy)-7-methoxy-4-chloro quinazoline (200 gm) were stirred for 15 minutes at 25-30° C., then a solution of 4-fluoro-3-chloroaniline in methanol (213 gm in 400 ml) was charged and refluxed for 6 hours. The reaction mass was cooled to 15-20° C., hydrochloric acid (40 ml) was added drop wise, and stirred at 5-10° C. for 30 minutes. The solid obtained was filtered and washed with chilled methanol (150 ml). The solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume), the reaction mass was concentrated to half the volume and cooled to 5-10° C. The solid obtained was filtered, washed with toluene (200 ml) and dried at 45-50° C. to yield the title compound (183 gm, 70% yield).

後処理

  1. temperaturerefluxed for 6 hours
  2. customThe solid obtained
  3. filtrationwas filtered
  4. washwashed with chilled methanol (150 ml)
  5. dissolutionThe solid was dissolved in a mixture of toluene (30 volume) and methanol (5 volume)
  6. concentrationthe reaction mass was concentrated to half the volume
  7. temperaturecooled to 5-10° C
  8. customThe solid obtained
  9. filtrationwas filtered
  10. washwashed with toluene (200 ml)
  11. customdried at 45-50° C.

出典と根拠

ORDレコード
ord-02050b8511364e229b559e46964bf720
出典データセット
uspto-grants-2013_01
特許番号
US08350029B2

反応ノート

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