Methanol → 7-Benzamido-1-(1-piperazinyl)-naphthalene

HRID 235117ノート

反応式

HRID 235117 の反応式
[C:1]([NH:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[CH:15][CH:16]=[C:17]2[N:20]2[CH2:25][CH2:24][N:23](C)[CH2:22][CH2:21]2)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OC(Cl)C)=O.CO>C(Cl)Cl>[C:1]([NH:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[CH:15][CH:16]=[C:17]2[N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 887MethanolHCID 5213051-Chloroethyl chloroformate2 回HCID 99611507-Benzamido-1-(4-methyl-1-piperazinyl)-naphthalene

生成物 1

HCID 189675377-Benzamido-1-(1-piperazinyl)-naphthalene収率 66.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

The title product from Example 1 (0.50 g, 1.45 mmol) was dissolved in methylene chloride (10 mL) and chilled to 0° C. 1-chloroethyl chloroformate (0.156 mL, 1.45 mmol) was added via syringe. The mixture was allowed to come to room temperature and then refluxed 3 hours. Additional 1-chloroethyl chloroformate (0.1 mL, 0.93 mmol) was added and the mixture was further refluxed overnight. Methanol (10mL) was added and the reaction was refluxed for 2 hours. The mixture was concentrated and the residue was taken up in methylene chloride and extracted with 1N NaOH and brine. The organic phase was dried, concentrated onto silica gel, and flash chromatographed (1×4 inches silica gel). Gradient elution with ethyl acetate/hexane of from 1: 1 to 100% ethyl acetate followed by elution with 2 to 10% ethanol/0.1% ammonium hydroxide/ethyl acetate gave recovered unweighed starting material. Continued elution with 15% methanol/0.1% ammonium hydroxide/ethyl acetate gave 0.32 g of the title product as a clear colorless oil which partially crystallized on standing. Trituration with ether gave 0.13 g (27%) of the title compound as white crystals: mp 141.5°-144° C.; 1H NMR δ 8.58 (br s, 1H), 8.04 (br s, 1H), 7.95 (dd, J=8, 1.5 Hz, 2H), 7.84 (d, J=9 Hz, 1H), 7.68 (dd, J=2, 9 Hz, 1H), 7.62-7.49 (m, 4H), 7.37 (t, J=8 Hz, 1H), 7.12 (d, J=7 Hz, 1H), 3.32-3.22 (m, 5H), 3.16 (br s, 3H), 2.40 (br s, 1H, exchanges with D2O). HRMS m/e calculated for C21H21N3O: 331.1680. Observed m/e: 331.1682.

後処理

  1. customto come to room temperature
  2. temperaturerefluxed 3 hours
  3. temperaturethe mixture was further refluxed overnight
  4. temperaturethe reaction was refluxed for 2 hours
  5. concentrationThe mixture was concentrated
  6. extractionextracted with 1N NaOH and brine
  7. customThe organic phase was dried
  8. concentrationconcentrated onto silica gel, and flash
  9. customchromatographed (1×4 inches silica gel)
  10. washGradient elution with ethyl acetate/hexane of from 1
  11. wash1 to 100% ethyl acetate followed by elution with 2 to 10% ethanol/0.1% ammonium hydroxide/ethyl acetate
  12. customgave
  13. customrecovered unweighed
  14. washelution with 15% methanol/0.1% ammonium hydroxide/ethyl acetate

出典と根拠

ORDレコード
ord-e109430247fa4672ae61aa78f181be72
出典データセット
uspto-grants-1997_01
特許番号
US05597826

反応ノート

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