Trifluoroacetic acid → HCID 178509455, 화합물

HRID 497930

반응식

HRID 497930 반응식
[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.FC(F)(F)C(O)=O.ClC(Cl)(Cl)C(OC(=O)C(Cl)(Cl)Cl)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[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

참가 물질

8

반응물 6

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 20079Trichloroacetic anhydrideHCID 764281H-Imidazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10740273(R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile

생성물 1

HCID 178509455HCID 178509455, 화합물수율 90.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
2.5 °C

실험 절차

In a 500 mL flask was charged (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile (25.0 g, 1 eq.), imidazole-4-carboxaldehyde (6.45 g, 1.1 eq.), and CH2Cl2 (150 mL) at room temperature. Cool to 0-5° C. Add trifluoroacetic acid (18.8 mL, 4 eq.) in a period of 10 min. A solution was obtained after addition. Stir the mixture for 10 min at 2° C. Add trichloroacetic acid anhydride (11.7 mL, 1.05 eq.) in a period of 20 min at 2° C. Stir the mixture for 30 min at 0-5° C. Add Na(OAc)3BH (15.51 g, 1.2 eq.) in two portions at 0-5° C. Agitate the mixture at 0° C. for 1.5 h, then room temperature for 1 hour. Add CH2Cl2 (100 mL), then cool to 0° C. Adjust the pH to 8-9 with 10% NaOH (about 125 mL used). Stir for 30 min. Separate the two phases. Wash the organic phase with H2O (2×100 mL), then separate the two phases. Remove most of the solvents, and add EtOH (200 mL); and heat up to 74° C. Stir for 10 min at 74° C. Cool to room temperature in a period of 60 min. Crystals appeared at 65° C. Filter and wash the crystals with EtOH (40 mL). Dry at 40° C. in vacuum oven over night to give the product (13.55 g, 90.7% yield) as a white solid.

후처리

  1. customA solution was obtained
  2. additionafter addition
  3. stirringStir the mixture for 30 min at 0-5° C
  4. customat 0-5° C
  5. stirringAgitate the mixture at 0° C. for 1.5 h
  6. waitroom temperature for 1 hour
  7. stirringStir for 30 min
  8. customSeparate the two phases
  9. washWash the organic phase with H2O (2×100 mL)
  10. customseparate the two phases
  11. customRemove most of the solvents
  12. additionadd EtOH (200 mL)
  13. temperatureand heat up to 74° C
  14. stirringStir for 10 min at 74° C
  15. temperatureCool to room temperature in a period of 60 min
  16. customappeared at 65° C
  17. filtrationFilter
  18. washwash the crystals with EtOH (40 mL)
  19. customDry at 40° C. in vacuum oven over night

출처 및 근거

ORD 기록
ord-8648a74a9ba0416bb1c0ef16a0a47619
출처 데이터셋
uspto-grants-2005_09
특허 번호
US06949642B2

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