تفاعل #972296

معادلة التفاعل

solution

N-[2-fluoro-5-(trifluoromethyl)phenyl]-N′-{4-[2-(3-hydroxypyrrolidin-3-yl)-1,3-thiazol-5-yl]phenyl}urea

acetic acid

formaldehyde

→

title compound

N-[2-fluoro-5-(trifluoromethyl)phenyl]-N′-{4-[2-(3-hydroxy-1-methylpyrrolidin-3-yl)-1,3-thiazol-5-yl]phenyl}urea

المذيبات

methanol

ظروف التفاعل

المعالجة

1. 1
   ترشيحThe reaction was then filtered
2. 2
   تركيزconcentrated under reduced pressure
3. 3
   أخرىThe residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography)
4. 4
   أخرىanalyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min)
5. 5
   workup.ADDITIONThe fractions containing the desired product
6. 6
   workup.ADDITIONwere diluted with saturated aqueous NaHCO3
7. 7
   استخلاصextracted with ethyl acetate
8. 8
   تجفيفThe organic layer was dried with anhydrous Na2SO4
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated under reduced pressure

الإجراء التجريبي

To an ambient solution of Example 14 (0.050 g, 0.107 mmol) in methanol containing 1% v/v acetic acid 1 mL) was added formaldehyde (0.012 mL, 0.161 mmol, 37 wt % in H2O) and MP-CNBH3 (0.054 g, 0.161 mmol, 3.0 mmol/g). The reaction was heated to 50° C. and shaken for 16 h. The reaction was then filtered and concentrated under reduced pressure. The residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min). The fractions containing the desired product were diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 2.01-2.13 (m, 1H), 2.25-2.33 (m, 3H), 2.35-2.46 (m, 1H), 2.51-2.58 (m, 1H), 2.73-2.94 (m, 3H), 6.22-6.31 (m, 1H), 7.37-7.44 (m, 1H), 7.47-7.56 (m, 3H), 7.56-7.62 (m, 2H), 7.98 (s, 1H), 8.62 (m, 1H), 8.92 (m, 1H), 9.32 (s, 1H); MS (ESI) m/z 481 [M+H]+.

المصدر