Diisopropylethylamine → 3-{[2-[2,6-Bis(isopropyl)phenoxycarbonyl]-benzoyl]amino}-propanoic Acid

To a solution containing (102) (2.1 g, 6.4 mmol) and beta-alanine tert-butyl ester hydrochloride (1.16 g, 6.4 mmol) in DMF (20 mL) was added diisopropylethylamine (2.4 mL, 13.7 mmol) followed by O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.5 g, 6.5 mmol). The resulting reaction mixture was stirred at room temperature for 14 h, diluted with ethyl acetate (100 mL), washed with 10% aqueous citric acid solution (5mL), followed by saturated aqueous NaHCO3 solution (50 mL) and brine (2×50 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The crude residue was dissolved in anhydrous dichloromethane (30 mL) and cooled to 0° C. before a solution of hydrochloric acid (10 mL, 4 N in dioxane) was added. The reaction was stirred for 1 h at 0° C. and 1 h at room temperature. The solvent was removed in vacuo and the crude residue was purified by preparative LC/MS to afford 0.85 g (38% yield over three steps) of the title compound (101). 1H NMR (400 MHz, CD3OD): δ 8.20 (dd, J=7.6, 0.8 Hz, 1H), 7.70-7.68 (m, 1H), 7.63-7.59 (m, 1H), 7.49 (dd, J=7.6, 0.8 Hz, 1H), 7.22-7.17 (m, 3H), 3.54 (t, J=7.2 Hz, 2H), 3.06-3.00 (m, 2H), 2.57 (t, J=6.8 Hz, 2H), 1.19 (d, J=6.8 Hz, 12H). MS (ESI) m/z 398.3 (M+H+).

1. customThe resulting reaction mixture
2. washwashed with 10% aqueous citric acid solution (5mL)
3. dry with materialThe organic phase was dried over MgSO4
4. concentrationconcentrated in vacuo
5. dissolutionThe crude residue was dissolved in anhydrous dichloromethane (30 mL)
6. temperaturecooled to 0° C. before a solution of hydrochloric acid (10 mL, 4 N in dioxane)
7. additionwas added
8. stirringThe reaction was stirred for 1 h at 0° C. and 1 h at room temperature
9. customThe solvent was removed in vacuo
10. customthe crude residue was purified by preparative LC/MS

ORD 기록

ord-d8421a9c4557429dbc6ddb9e774ac570

출처 데이터셋

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07576127B2