تفاعل #42138

معادلة التفاعل

4-(N-tert-butoxycarbonylaminomethyl)aniline

3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid

HATU

DIPEA

→

title intermediate

المردود 94.0%

Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

المردود 94.0%

المذيبات

TFA DCM

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent was removed under reduced pressure
2. 2
   workup.DISSOLUTIONThe resulting residue was dissolved in DCM (20 mL)
3. 3
   غسيلwashed with saturated aqueous sodium bicarbonate solution (10 mL)
4. 4
   تجفيفThe organic phase was then dried over MgSO4
5. 5
   أخرىthe solvent was removed under reduced pressure
6. 6
   أخرىThe crude product was purified by flash chromatography (5-10% MeOH/DCM)
7. 7
   أخرىto give a solid, which
8. 8
   workup.STIRRINGstirred at room temperature for 2 hours
9. 9
   أخرىThe solvent was then removed under reduced pressure
10. 10
    workup.DISSOLUTIONthe crude residue was dissolved in DCM (30 mL)
11. 11
    غسيلwashed with 1N NaOH (15 mL)
12. 12
    أخرىThe organic phase was separated
13. 13
    تجفيفdried over MgSO4
14. 14
    ترشيحfiltered
15. 15
    أخرىthe solvent was removed under reduced pressure

الإجراء التجريبي

To a stirred solution of 4-(N-tert-butoxycarbonylaminomethyl)aniline (756 mg, 3.4 mmol), 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (1.5 g, 4.08 mmol; prepared as described in Preparation 11) and HATU (1.55 g, 4.08 mmol) in DMF (6.8 mL), was added DIPEA (770 mL, 4.42 mmol). The reaction mixture was stirred at 50° C. overnight, and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic phase was then dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (5-10% MeOH/DCM) to give a solid, which was dissolved in TFA/DCM (25%, 30 mL) and stirred at room temperature for 2 hours. The solvent was then removed under reduced pressure and the crude residue was dissolved in DCM (30 mL) and washed with 1N NaOH (15 mL). The organic phase was separated, dried over MgSO4, filtered and the solvent was removed under reduced pressure to give 1.5 g of the title intermediate (94% yield over 2 steps).

المصدر