反应详情

To a solution of (2R,4S)-5-Biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester (32 mg, 0.065 mmol) in dichloromethane (1 mL) is added DBU (24 mg, 0.164 mmol). After stirring for 3 hours, additional DBU (24 mg, 0.146 mmol) is added. After stirring for 2 hours, the reaction mixture is diluted with dichloromethane and washed with saturated aqueous NH4Cl. The organic layer is dried over Na2SO4 and concentrated. The residue is dissolved in MeOH and treated with aqueous 2M NaOH. After stirring for 1 hours, the reaction mixture is diluted with ethyl acetate and acidified with aqueous 1M HCl. The mixture is extracted with ethyl acetate and washed with brine. The organic layer is dried over Na2SO4 and concentrated. The residue is purified by reverse phase HPLC (0.1% TFA-H2O/MeCN) to give (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(3-1H-tetrazol-5-yl-propionylamino)-pentanoic acid (14 mg). HPLC Retention time 1.17 minutes (condition C); MS 408.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03 (d, J=7.07 Hz, 3H), 1.34 (ddd, J=4.80, 10.11, 14.91 Hz, 1H), 1.78 (ddd, J=4.04, 9.60, 13.64 Hz, 1H), 2.31-2.42 (m, 1H), 2.52-2.59 (m, 2H), 2.68 (d, J=7.07 Hz, 2H), 3.03 (dd, J=7.58, 7.58 Hz, 2H), 3.90-4.01 (m, 1H), 7.20 (d, J=8.08 Hz, 2H), 7.34 (t, J=9.09 Hz, 1H), 7.45 (d, J=7.83 Hz, 2H), 7.55 (d, J=8.34 Hz, 2H), 7.64 (d, J=7.33 Hz, 2H), 7.84 (d, J=8.34 Hz, 1H), 11.99 (bs, 1H).

1. stirringAfter stirring for 2 hours
2. washwashed with saturated aqueous NH4Cl
3. dry with materialThe organic layer is dried over Na2SO4
4. concentrationconcentrated
5. dissolutionThe residue is dissolved in MeOH
6. additiontreated with aqueous 2M NaOH
7. stirringAfter stirring for 1 hours
8. additionthe reaction mixture is diluted with ethyl acetate
9. extractionThe mixture is extracted with ethyl acetate
10. washwashed with brine
11. dry with materialThe organic layer is dried over Na2SO4
12. concentrationconcentrated
13. customThe residue is purified by reverse phase HPLC (0.1% TFA-H2O/MeCN)