Trichloroacetic Acid → HCID 178509455, compound

Temperature

2.5 °C

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.

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

ORD record

ord-af42dd4e25a54980850401eca4617d39

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949642B2