Reacción #9058

Ecuación de reacción

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

piperonal

AcOH

NaBH(OAc)3

→

titled compound

Rendimiento 33.1%

benzo[1,3]dioxol-5-ylmethyl-(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

Rendimiento 33.1%

Disolventes

THF

CH2Cl2

trifluoroacetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónthe reaction mixture was concentrated
2. 2
   workup.DISSOLUTIONredissolved in H2O (˜2 mL)
3. 3
   ExtracciónThe aqueous solution was extracted with CH2Cl2 (3×50 mL)
4. 4
   Secadothe combined organic extracts were dried over MgSO4
5. 5
   Concentraciónconcentrated to a yellow syrup
6. 6
   OtroThe product was purified by column chromatography on silica gel (100:1:1—EtOAc:MeOH:NH4OH)

Procedimiento

Using General Procedure B: To a solution of [1-(tert-butoxycarbonyl)-(1H-benzimidazol-2-ylmethyl)]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (125 mg, 0.33 mmol), piperonal (50 mg, 0.33 mmol) and AcOH (0.02 mL, 0.33 mmol) in THF (3.3 mL) was added NaBH(OAc)3 (210 mg, 0.99 mmol) and the resultant suspension stirred at room temperature for 16 h. The crude product was dissolved in a mixture of CH2Cl2 (˜2 mL) and trifluoroacetic acid (˜2 mL). After 1.5 h, the reaction mixture was concentrated, redissolved in H2O (˜2 mL), and basified with 1N NaOH. The aqueous solution was extracted with CH2Cl2 (3×50 mL) and the combined organic extracts were dried over MgSO4 and concentrated to a yellow syrup. The product was purified by column chromatography on silica gel (100:1:1—EtOAc:MeOH:NH4OH) to give the titled compound as a white foam (45 mg, 33%). 1H NMR (300 MHz, CDCl3) δ 8.69 (d, 1H, J=3.3 Hz), 7.58 (br s, 2H), 7.43 (d, 1H, J=7.2 Hz), 7.21–7.16 (m, 3H), 6.99 (d, 1H, J=1.57 Hz), 6.79 (dd, 1H, J=8.1, 1.5 Hz), 6.65 (d, 1H, J=7.8 Hz), 5.86–5.85 (m, 2H), 4.15 (d, 1H, J=16.5 Hz), 4.09–4.06 (m, 1H), 3.98 (d, 1H, J=16.8 Hz), 3.64 (s, 2H), 2.91–2.80 (m, 1H), 2.74–2.67 (m, 1H), 2.27–2.17 (m, 1H), 2.06–1.64 (m, 2H), 1.75–1.64 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ 159.2, 158.0, 149.4, 148.7, 148.5, 139.0, 136.5, 135.0, 124.0, 123.5, 123.3, 110.7, 109.5, 102.5, 61.8, 55.5, 49.9, 31.0, 25.0, 23.1. ES-MS m/z 413.3 (M+H). Anal Calcd for (C25H24N4O2).0.8(H2O): C, 70.34; H, 6.04; N, 13.12. Found: C, 70.29; H, 5.99; N, 12.75.

Fuente