Trichloroacetic Acid → HCID 178509455、化合物

HRID 497932

反応式

HRID 497932 の反応式
[C:1]1([CH2:7][C@H:8]2[N:14]([S:15]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)(=[O:17])=[O:16])[CH2:13][C:12]3[CH:23]=[C:24]([C:27]#[N:28])[CH:25]=[CH:26][C:11]=3[NH:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:29]1[CH:33]=[C:32]([CH:34]=O)[N:31]=[CH:30]1.ClC(Cl)(Cl)C(O)=O.ClC(Cl)(Cl)C(OC(=O)C(Cl)(Cl)Cl)=O.C([SiH](CC)CC)C.[OH-].[Na+]>C(Cl)Cl>[NH:29]1[CH:33]=[C:32]([CH2:34][N:10]2[C:11]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][C:12]=3[CH2:13][N:14]([S:15]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)(=[O:17])=[O:16])[C@H:8]([CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:9]2)[N:31]=[CH:30]1

参加物

8

反応物 6

HCID 6421Trichloroacetic AcidHCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 20079Trichloroacetic anhydrideHCID 764281H-Imidazole-4-carbaldehydeHCID 10740273(R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile

生成物 1

HCID 178509455HCID 178509455、化合物収率 85.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
2.5 °C

実験手順

In a 500 mL flask was charged (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile (20.0 g, 1 eq.), imidazole-4-carboxaldehyde (5.2 g, 1.1 eq.), and CH2Cl2 (80 mL) at room temperature. Cool to 0-5° C. Add trichloroacetic acid (32 g, 4 eq.) and trichloroacetic acid anhydride (12.2 mL, 1.36 eq.) while keeping the temperature below 20° C. Stir the mixture for 30 min at 0-5° C. Add Triethylsilane (11.6 mL, 1.5 eq.). Agitate the mixture at 20-25° C. for 26 h until the reaction is complete. Add CH2Cl2 (80 mL), then cool to 0° C. Adjust the pH to 8-9 with 10% NaOH. Separate the two phases. Wash the organic phase with H2O (50 mL). Remove most of the solvents, and add EtOH (150 mL); and heat up to reflux and stir at reflux for 10 min. Cool to room temperature in a period of 60 min. Crystals appeared at 65° C. Stir at room temperature for 2 h. Filter and wash the crystals with EtOH (150 mL). Dry at 40° C. in vacuum oven over night to give the product (20.4 g, 85% yield) as a white solid.

後処理

  1. customthe temperature below 20° C
  2. stirringAgitate the mixture at 20-25° C. for 26 h until the reaction
  3. customSeparate the two phases
  4. washWash the organic phase with H2O (50 mL)
  5. customRemove most of the solvents
  6. additionadd EtOH (150 mL)
  7. temperatureand heat up
  8. temperatureto reflux
  9. stirringstir
  10. temperatureat reflux for 10 min
  11. temperatureCool to room temperature in a period of 60 min
  12. customappeared at 65° C
  13. stirringStir at room temperature for 2 h
  14. filtrationFilter
  15. washwash the crystals with EtOH (150 mL)
  16. customDry at 40° C. in vacuum oven over night

出典と根拠

ORDレコード
ord-af42dd4e25a54980850401eca4617d39
出典データセット
uspto-grants-2005_09
特許番号
US06949642B2

関連ノート

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