Synthesis process of barnidipine hydrochloride

A technology of barnidipine hydrochloride and synthesis process, which is applied in the fields of drug combination, cardiovascular system diseases, organic chemistry, etc. low cost effect

A technology of barnidipine hydrochloride and synthesis process, which is applied in the fields of drug combination, cardiovascular system diseases, organic chemistry, etc. low cost effect

CN101643469AActive Publication Date: 2010-02-10WUHAN BIOCAUSE PHARMA DEV
1 Cites 18 Cited by

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis process of barnidipine hydrochloride
  • Synthesis process of barnidipine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0035] The specific implementation steps are as follows:

[0036] 1. In a dry 500ml single-necked flask, add 3-hydroxypropionitrile (117g, 1.648mol) and 4g of triethylamine, raise the temperature to 80°C, then slowly add diketene (159.0g, 1.892mol) dropwise. After stirring for more than 6 hours, the low boiling point substances were evaporated to obtain 137 g of a reddish-brown oily substance, which was compound (VI), with a yield of 54%.

[0037] 2. In a dry 2000ml single-necked flask, add m-nitrobenzaldehyde 67.5g (0.447mol), compound (VI) 69.3g (0.447mol), ammonium acetate 5g, isopropanol 318g, and stir at room temperature for 15 hours , a large amount of white solid was formed in the reaction. After the reaction was completed, 104 g of white solid was obtained by filtration, which was compound (VII), and the yield was 80.8%.

[0038] 3. 74.9 g (0.26 mol) of compound (VII), 30 g (0.26 mol) of methyl β-aminocrotonate and 180 ml of methanol were refluxed for 2 hours. After...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a synthesis process of barnidipine hydrochloride. The synthesis process comprises the following steps: (1) reacting 3-hydroxypropionitrile (I) with ketene dimer (II) to obtaina compound (VI); (2) reacting the compound (VI) with m-nitrobenzaldehyde (III) to obtain a compound (VII); (3)reacting the compound (VII) with beta-amion ethyl crotonate (IV) to obtain a compound (VIII); (4) hydrolyzing the compound (VIII) by an alkali to obtain a compound (IX); (5) resolving the compound (IX) with a chiral organic base to obtain a compound (X); (6) carrying out a reaction between the compound (X) and benzyl pyrrole alcohol to obtain a compound (XI); and (7) adding the compound (XI) in a chlorine hydride solution to obtain barnidipine hydrochloride (XII). The synthesis process has the following advantages: (1) mild reaction conditions, easily separated and purified products obtained in every step, which has controllable quality, (2) higher yield in each step, easily obtainable raw and auxiliary materials, low total cost, (3) no column chromatography and industrialized production suitability.

Description

Technical field: [0001] The invention belongs to the field of production of fine chemical or pharmaceutical chemical products, and in particular relates to a synthesis process of a novel antihypertensive drug barnidipine hydrochloride. Background technique: [0002] The chemical name of Barnidipine Hydrochloride (CAS: 104757-53-1) is (S)-3-((S)-1-benzylpyrrolidinyl)-2,6-dimethyl-4- (3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride, the structural formula is: [0003] [0004] Barnidipine hydrochloride is a new type of long-acting dihydropyridine calcium ion antagonist for the treatment of essential hypertension and renal hypertension. This product is the first single optical isomer in this class of drugs. It has a high degree of vascular selectivity, can relax blood vessels, increase coronary blood flow, and lower blood pressure. ; This product has less toxic and side effects, and can reduce myocardial inhibition compared with similar drugs, so it is w...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
10 Feb 2010
Publication
CN101643469A
IPC
C07D401/12; A61P9/12
Inventors
李立威; 程志刚