HRID1774368

反应详情

EQUATION

反应方程式

HRID 1774368 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

1

CONDITIONS

反应条件

温度
0 °C

PROCEDURE

实验过程

To a mixture of 1-(4-(2-aminopyridin-4-yloxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (40 mg, 0.08 mmol) and DIPEA (69 μL, 0.40 mmol) in THF (5.0 mL) at 0° C. under N2 was added acetyl chloride (22 μL, 0.08 mmol) and the mixture maintained at 0° C. for 30 min and then warmed to RT for 16 hr. The reaction was quenched by the addition of a solution of NH3 in MeOH (1% w/v, 2.0 mL) and after 45 min at RT the volatiles were evaporated in vacuo. The residue was subjected to purification by SCX capture and release and then by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-70%, gradient elution). The impure material so obtained was subjected to re-purification by SCX capture and release and by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-65%, gradient elution) to afford the title compound, Example 3, as a white solid (12 mg, 27%); Rt 2.26 min (Method 2); m/z 549 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (9H, s), 2.01 (3H, s), 2.38 (3H, s), 6.39 (1H, s), 6.63 (1H, dd), 7.31 (1H, d), 7.36 (2H, d), 7.48 (2H, d), 7.56 (1H, m), 7.61-7.66 (2H, overlapping m), 7.83 (1H, d), 7.96 (1H, d), 8.16 (1H, d), 8.19 (1H, d), 9.02 (1H, s), 9.30 (1H, s), 10.52 (1H, s).

WORKUP

后处理

  1. temperaturewarmed to RT for 16 hr
  2. customThe reaction was quenched by the addition of a solution of NH3 in MeOH (1% w/v, 2.0 mL) and after 45 min at RT the volatiles
  3. customwere evaporated in vacuo
  4. customThe residue was subjected to purification by SCX capture and release
  5. washby flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-70%, gradient elution)
  6. customThe impure material so obtained
  7. customwas subjected to re-purification by SCX capture and release and by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-65%, gradient elution)