Reacción #9047

Ecuación de reacción

sodium bicarbonate

(1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

methyl 4-formylbenzoate

NaBH(OAc)3

→

title compound

Rendimiento 74.0%

4-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid methyl ester

Rendimiento 74.0%

Disolventes

TFA

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGstirred 3 h
2. 2
   Extracciónthe resulting mixture was extracted with CH2Cl2 (3×20 mL)
3. 3
   Secadothe combined organic extracts were dried (MgSO4)
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   OtroPurification of the crude material by flash chromatography (silica gel, 50:2:1 CH2Cl2/MeOH/NH4OH)

Procedimiento

Following General Procedure B: To a solution of (1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (680 mg, 1.8 mmol) and methyl 4-formylbenzoate (295 mg, 1.8 mmol) in CH2Cl2 (10 mL) was added NaBH(OAc)3 (763 mg, 3.6 mmol) and the mixture stirred for 18 h. The resulting crude material was taken up in neat TFA (2 mL) and stirred 3 h. Saturated aqueous sodium bicarbonate (10 mL) was cautiously added, and the resulting mixture was extracted with CH2Cl2 (3×20 mL), and the combined organic extracts were dried (MgSO4), and concentrated in vacuo. Purification of the crude material by flash chromatography (silica gel, 50:2:1 CH2Cl2/MeOH/NH4OH) afforded the title compound (565 mg, 74%) as a white solid. 1H NMR (CDCl3) δ 1.64–1.75 (m, 1H), 2.01–2.08 (m, 2H), 2.26–2.28 (m, 1H), 2.74–2.76 (m, 1H), 2.81–2.86 (m, 1H), 3.81 (s, 2H), 3.86 (s, 3H), 3.94 (d, 1H, J=17 Hz), 4.09 (dd, 1H, J=9, 7 Hz), 4.21 (d, 1H, J=17 Hz), 7.18–7.22 (m, 3H), 7.44 (br d, 1H, J=8 Hz), 7.49 (d, 2H, J=8 Hz), 7.50–7.53 (m, 1H), 7.64–7.66 (m, 1H), 7.91 (d, 2H, J=8 Hz), 8.70 (dd, 1H, J=5, 1 Hz); 13C NMR (CDCl3) δ 21.2, 23.6, 29.0, 48.7, 51.9, 53.7, 111.0, 118.6, 121.5, 122.3, 129.3, 128.9, 129.5, 134.7, 137.2, 144.8, 146.8, 155.7, 157.1, 166.8. ES-MS m/z 427 (M+H). Anal. Calcd. for C26H26N4O2.0.6H2O.0.3CH2Cl2: C, 68.26; H, 6.05; N, 12.11. Found: C, 68.57; H, 6.12; N, 11.75.

Fuente