تفاعل #426416

معادلة التفاعل

HOAt

(S)-methyl 2-((S)-2-amino-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

(S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid

EDC

NaHCO3

NMM

→

title compound

المردود 100.0%

(S)-Methyl 2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

المردود 100.0%

المذيبات

DMF

EtOAc

ظروف التفاعل

المعالجة

1. 1
   أخرىthe resulting reaction mixture
2. 2
   درجة الحرارةwarmed to room temperature
3. 3
   workup.STIRRINGstirred for 4 h
4. 4
   workup.ADDITIONThe reaction mixture was then poured into a separatory funnel
5. 5
   استخلاصThe aqueous layer was extracted with EtOAc (3×)
6. 6
   غسيلThe combined organic extracts were washed with 1N HCl (2×) and 10% LiCl
7. 7
   تجفيفdried over MgSO4
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated in vacuo

الإجراء التجريبي

To a 0° C. solution of (S)-methyl 2-((S)-2-amino-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (966 mg, 2.02 mmol) and (S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid (Advanced ChemTech, 411 mg, 2.02 mmol) in DMF (20 mL) was added EDC (465 mg, 2.43 mmol), followed by HOAt (330 mg, 2.43 mmol). NMM (667 μl, 6.07 mmol) was then added, and the resulting reaction mixture was stirred at 0° C. for 30 min, then warmed to room temperature and stirred for 4 h. The reaction mixture was then poured into a separatory funnel containing EtOAc and sat. aq. NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with 1N HCl (2×) and 10% LiCl, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (1.34 g, 2.02 mmol, 100%) as a light yellow foam, which was used without further purification. MS (ESI+) m/z 663.3 (M+H)+.

المصدر