Parecoxib derivative as well as preparation method and application thereof
A technology of compounds and solvates, applied in the field of pharmaceutical compounds, can solve problems such as precipitation
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Examples
Synthetic example 1
[0085]
[0086] K 2 CO 3 (375mg, 2.7mmol, 5.0eq), methyl chloroacetate (1.16g, 10.8mmol, 20eq), the reaction was stirred at room temperature for 18 hours. with H 2 The reaction mixture was diluted with O (20 mL), extracted with EtOAc (20 mL x 2). The combined organic phases were washed with saturated brine (15 mL), washed with Na 2 SO 4 After drying, filter and concentrate in vacuo. The obtained crude product residue was purified by TLC (PE / EA=1.7:1) to obtain 50 mg of crude product, which was purified by prep-HPLC (0.1% HCOOH / H in ACN 2 O) Further purification gave white solid compound 1 (16.65 mg, yield 6%).
[0087] LCMS: (M+H)+: 443.1
[0088] 1 H-NMR (400MHz, CDCl3) δ = 8.00 (m, 2H), 7.38 (m, 7H), 5.91 (s, 2H), 2.61 (q, J = 7.2Hz, 2H), 2.52 (s, 3H), 2.08(s,3H),1.10(t,J=7.2Hz,3H).
Synthetic example 2
[0090]
[0091] K 2 CO 3 (746mg, 5.41mmol, 1.54eq), chloromethyl isopropyl carbonate (4mL), and the reaction was stirred at room temperature for 18 hours. with H 2 The reaction mixture was diluted with O (30 mL), extracted with EtOAc (40 mL×3). The combined organic phases were washed with saturated brine (30mL×3), washed with Na 2 SO 4 It was dried, filtered, and concentrated to obtain a crude residue, which was purified by TLC (EtOAc:PE=1:2) to obtain white solid Example 2 (104.4 mg, yield 33.73%). LCMS: (M+H)+: 487.2
[0092] 1 H-NMR (400MHz, DMSO-d6) δ = 8.01-7.94 (m, 2H), 7.50-7.39 (m, 5H), 7.35-7.30 (m, 2H), 5.91 (s, 2H), 4.87-4.71 ( m,1H),2.65(dd,J=7.1Hz,2H),2.49(s,3H),1.23(d,J=6.2Hz,6H),0.92(t,J=7.2Hz,3H).
[0093] Synthetic Example 3.
[0094]
[0095] DIPEA (174mg, 1.35mmol, 2.5eq), methyl chloromethyl carbonate (134.4mg, 1.08mmol, 2.0eq), the reaction was stirred at room temperature for 18 hours. Spin dry with H 2 The reaction mixture was diluted wi...
Embodiment 1
[0103] Synthesize following compound 5-28 with reference to embodiment 1
[0104] List of specific examples
[0105]
[0106]
[0107]
[0108] Also included within the scope of the present invention is a pharmaceutical combination comprising said active compound in admixture with one or more non-toxic pharmaceutically acceptable carriers and / or diluents and / or adjuvants (hereinafter collectively referred to as "carrier" materials) substances, which may also contain other pharmaceutically active ingredients as required. The active compound of the present invention can be administered orally or externally, preferably in the form of a drug combination suitable for the administration route and at an effective dose required for treatment.
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Description
Claims
Application Information
- IPC
- C07D261/08; C07F9/653; A61P29/00; A61P1/02; A61P19/02; A61K31/42; A61K31/675
- CPC
- A61P1/02; A61P19/02; A61P29/00; C07D261/08; C07F9/653
- Inventors
- 朱加望; 王泽根