반응 #730013

반응 방정식

(R)-1-carboxy-2-(3,4-dimethyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

TBTU

triethylamine

tert.-butyl (4-methyl-[1,4′]bipiperidinyl-4-yl)-carbamate

TFA

→

(R)-2-(4-amino-4-methyl-1,4′-bipiperidinyl-1′-yl)-1-(3,4-dimethyl-2-oxo-2,3-dihydro-benzoxazol-6-ylmethyl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

용매

DMF

DCM

DCM

반응 조건

후처리

1. 1
   기타The reaction mixture was purified by HPLC
2. 2
   workup.ADDITIONthe fractions containing the product
3. 3
   기타The residue obtained
4. 4
   기타to evaporate off overnight
5. 5
   추출extracted twice with 2 mL DCM
6. 6
   기타purified by HPLC
7. 7
   workup.ADDITIONThe fractions containing the product

실험 절차

A solution of 80 mg (0.15 mmol) (R)-1-carboxy-2-(3,4-dimethyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 58 mg (0.18 mmol) TBTU, 140 μL (1.00 mmol) triethylamine and 59 mg (0.16 mmol) tert.-butyl (4-methyl-[1,4′]bipiperidinyl-4-yl)-carbamate in 1.8 mL DMF were stirred overnight at RT. The reaction mixture was purified by HPLC, the fractions containing the product were combined and lyophilised. The residue obtained was dissolved in 4 mL DCM, combined with 0.5 mL TFA and the reaction solution was stirred for 5 h at RT. The DCM was left to evaporate off overnight, the residue was combined with 2 mL 15% K2CO3 solution and extracted twice with 2 mL DCM. After the solvent had been eliminated the residue was taken up in 1 mL DMF and purified by HPLC. The fractions containing the product were combined and lyophilised.

출처