4-Methylmorpholine → (1S)-1-(4-Fluoro-1-phenyl-1H-benzimidazol-2-yl)ethan-1-amine

A mixture of 3-fluoro-N1-phenylbenzene-1,2-diamine (440 mg, 2.18 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (454 mg, 2.40 mmol), HOAt (327 mg, 2.40 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (460 mg, 2.40 mmol) and 4-methylmorpholine (0.527 mL, 4.79 mmol) in anhydrous DCM (20 mL) was stirred at RT for 2 h. The reaction mixture was diluted with DCM (100 mL) and washed with a saturated solution of NaHCO3. The organic layer was then dried and concentrated in vacuo. The resulting residue was dissolved in AcOH (10 mL) and heated to 70° C. for 2 h and then to 80° C. for 20 h. After cooling to RT, TFA (20 mL) was added and the mixture was stirred at RT for 1 h and 20 min. Volatiles were then removed in vacuo and the residue was dissolved in DCM (100 mL) and washed with a saturated solution of NaHCO3. The organic layer was then washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in TBME) affording (S)-1-(4-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine as a brown oil (396 mg, 71%). LCMS: RT 2.01 min [M−NH2]+ 239.1.

1. washwashed with a saturated solution of NaHCO3
2. customThe organic layer was then dried
3. concentrationconcentrated in vacuo
4. dissolutionThe resulting residue was dissolved in AcOH (10 mL)
5. temperatureheated to 70° C. for 2 h
6. waitto 80° C. for 20 h
7. temperatureAfter cooling to RT
8. additionTFA (20 mL) was added
9. stirringthe mixture was stirred at RT for 1 h and 20 min
10. customVolatiles were then removed in vacuo
11. dissolutionthe residue was dissolved in DCM (100 mL)
12. washwashed with a saturated solution of NaHCO3
13. washThe organic layer was then washed with brine
14. dry with materialdried (Na2SO4)
15. concentrationconcentrated in vacuo
16. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in TBME)

ORD 기록

ord-3cd03a71ec8f42d98a99b3d83abe8ce9

출처 데이터셋

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08653089B2