反应详情

Treat [2-(4-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester (534.3 mg, 2.2 mmol) with NaH (80% in mineral oil, 78.0 mg (2.6 mmol) in anhydrous DMF (10 mL) at room temperature for 30 minutes. Add 6-chloronicotinamide (343.8 mg, 2.2 mmol) and heat the mixture at 80° C. overnight. Quench the reaction with H2O and concentrate to dryness, using xylenes to remove DMF as an azeotrope. Suspend the residue in MeOH and filter with thorough MeOH and CH2Cl2 rinse. Concentrate the filtrate and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH. Deprotect the BOC group with 1:1 TFA/CH2Cl2 (16 mL) at room temperature overnight. Concentrate and purify by an SCX column, washing with MeOH and then eluting with 2.0 M NH3 in MeOH: MS ES+ 297.9 (M+H+K)+, HRMS calcd for Cl14H16N3O2 258.1243 (M+H)+, found 258.1235, time 0.40 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=6.93 min, 100% purity.

1. customQuench
2. customthe reaction with H2O
3. concentrationconcentrate to dryness
4. customto remove DMF as an azeotrope
5. filtrationfilter with thorough MeOH and CH2Cl2
6. washrinse
7. concentrationConcentrate the filtrate
8. custompurify by flash chromatography
9. washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH
10. customat room temperature
11. customovernight
12. concentrationConcentrate
13. custompurify by an SCX column
14. washwashing with MeOH
15. washeluting with 2.0 M NH3 in MeOH
16. custom258.1235, time 0.40 min
17. customHPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=6.93 min, 100% purity