反应详情

(3R,5S)-3-{Cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo-[1,4]oxazin-6-yl]-carbamoyl}-5-phenylacetylamino-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (90 mg, 0.12 mmol) is treated with 4N HCl/AcOEt (2 mL) at r.t. for 1 hr, then evaporated. The evaporated residue is dissolved in CH2Cl2 (1 mL). To the solution is added phenylacetyl chloride (20.4 mg, 0.132 mmol) and diisopropyl ethyl amine (32 mg, 0.264 mmol) at 0° C. and stirred for 40 min. After adding 1N HClaq, the mixture is extracted with CH2Cl2, washed with sat NaHCO3aq, brine and dried (MgSO4). Concentration under vacuum and the evaporated residue is dissolved in THF (1 mL). To the solution is added DBU (9 mg, 0.06 mmol) and N-(2-mercaptoethyl)aminoethyl polystyrene (2.1 mmol/g, 286 mg, 0.6 mmol) and stirred for 1 h at r.t. The reaction mixture is filtered via celite pad and washed with THF. Concentration under vacuum and purification with RP-HPLC gives the title compound. MS: 549 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 2.78 min.

1. customevaporated
2. dissolutionThe evaporated residue is dissolved in CH2Cl2 (1 mL)
3. additionAfter adding 1N HClaq
4. extractionthe mixture is extracted with CH2Cl2
5. washwashed
6. dry with materialdried (MgSO4)
7. concentrationConcentration under vacuum
8. dissolutionthe evaporated residue is dissolved in THF (1 mL)
9. stirringstirred for 1 h at r.t
10. filtrationThe reaction mixture is filtered via celite pad
11. washwashed with THF
12. concentrationConcentration
13. customunder vacuum and purification with RP-HPLC