Reacción #744462

Ecuación de reacción

(4-isopropoxy-phenyl)-carbamic acid 4-nitro-phenyl ester

4-{7-[3-(1H-Tetrazol-5-yl)-propoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid tert-butyl ester

TFA anisole

→

title compound

Rendimiento 14.0%

4-{7-[3-(1H-Tetrazol-5-yl)-propoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide

Rendimiento 14.0%

Disolventes

Pyridine

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe solution was then concentrated
2. 2
   workup.ADDITIONwere added
3. 3
   workup.STIRRINGthe solution was stirred at 80° C. for 15 min
4. 4
   ConcentraciónThe reaction was concentrated
5. 5
   Extracciónextracted with 95:5 DCM/MeOH (2×2 mL)
6. 6
   SecadoThe combined organic layers were dried (Na2SO4)
7. 7
   Concentraciónconcentrated
8. 8
   Otropurified by flash silica cartridge chromatography (EtOAc→acetone eluent)

Procedimiento

A solution of 4-{7-[3-(1H-Tetrazol-5-yl)-propoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid tert-butyl ester (6.1 mg, 14 μmol), as prepared in the previous step, in 9:1 TFA/anisole (100 μL) was stirred at 100° C. for 10 min. The solution was then concentrated. Pyridine (100 μL) and (4-isopropoxy-phenyl)-carbamic acid 4-nitro-phenyl ester (5.8 mg, 18 μmol), as prepared in Example 1a, were added, and the solution was stirred at 80° C. for 15 min. The reaction was concentrated, taken up in 1M NaH2PO4 (2 mL), and extracted with 95:5 DCM/MeOH (2×2 mL). The combined organic layers were dried (Na2SO4), concentrated, and purified by flash silica cartridge chromatography (EtOAc→acetone eluent) to provide the title compound (1.0 mg, 14%). 1H-NMR (400 MHz, 95:5 CDCl3/CD3OD) δ 9.09 (s, 1H), 8.08 (s, 1H), 7.30-7.21 (m, 4H), 6.85 (m, 2H), 4.49 (septet, 1H), 4.27 (m, 2H), 4.24 (t, 2H), 3.70 (tt, 1H), 3.19 (t, 2H), 3.12 (td, 2H), 2.40 (m, 2H), 2.17-1.92 (m, 4H), 1.32 (d, 6H). LC/MS (ESI) calcd mass 516.3, found 517.2 (MH)+.

Fuente