Raw material intermediate Enalapril Maleate Powder

CAS:76095-16-4

MF:C24H32N2O9

MW:492.52

EINECS:278-375-7

Specification​: 99% min Enalapril Maleate Powder

Sample:Enalapril Maleate Powder

Packaging:1kg/bag, 25kg/drum

Brand: Henrikang

Appearance: white to off-white

Storage: Cool Dry Place

Shelf Life: 2 Years

Test Method: HPLC

Enalapril Maleate Usage and Synthesis.

Enalapril maleate, a prescription drug, functions mainly in the treatment of all stages of essential hypertension, renal hypertension, congestive heart failure, etc.

Enalapril maleate is a potent angiotensin-converting enzyme (ACE) inhibitor without sulfhydryl groups, which is hydrolysed in vivo to Enalaprilat and exerts ACE inhibition.

Its mechanism of action is to inhibit the conversion of angiotensin Ⅰ into angiotensin Ⅱ, then the vascular smooth muscle tone is weakened, aldosterone secretion is reduced, and blood pressure falls.

Uses and functions of Enalapril Maleate.

All stages of essential hypertension; renal vascular hypertension; heart failure at all levels; in patients with symptomatic heart failure, it is also indicated to improve survival, slow the progression of symptomatic heart failure, and reduce hospitalisations due to heart failure; prevention of symptomatic heart failure, and, in patients with asymptomatic left ventricular (LV) insufficiency, prevention of coronary ischemic events in patients with LV insufficiency, and it is indicated to reduce the incidence of myocardial infarction, and to reduce hospitalisation due to stable angina. Reduce hospitalisation due to unstable angina.

It is a renin-angiotensin antihypertensive drug.

Pharmacological Effect of Enalapril Maleate.

Enalapril maleate is a potent angiotensin-converting enzyme (ACE) inhibitor without sulfhydryl groups, which is hydrolysed to enalaprilat in vivo and exerts ACE inhibition.

Its mechanism of action is to inhibit the conversion of angiotensin I into angiotensin II, which results in the weakening of vascular smooth muscle tone, the reduction of aldosterone secretion, and the decrease of blood pressure.

Its antihypertensive effect is 10 times stronger than that of captopril and more durable. Its antihypertensive effect is slow and long-lasting.

Its haemodynamic effect is similar to that of captopril, which can reduce total peripheral vascular resistance and renal vascular resistance and increase renal blood flow.

Long-term application can reverse left ventricular hypertrophy and improve ventricular remodelling.

Production Method of  Bulk Enalapril Maleate Powder.

Disodium hydrogen phosphate (20.4g, 2.0eq) was dissolved in 100mL of water, and when the system was dissolved clear, 160mL of dichloromethane was added, N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanine (20.0g, 1.0eq), and stirred at room temperature. Triphosgene (8.4g, 0.4eq) was dissolved in 40mL of dichloromethane and added dropwise to the reaction system at room temperature, after the dropwise completion of the reaction for 1h, 0.5mL of pyridine was added, stirred for 1h and left to separate, the organic phase was concentrated under reduced pressure to obtain an oil, dissolved in 16mL of dichloromethane, added dropwise to 200mL of n-heptane, stirred at 0-10°C to precipitate crystals for 1h, and then pumped and filtered under reduced pressure to obtain a white solid N-[(S) -1-ethoxycarbonyl-3-phenylpropyl]-L-alanine-N-carboxylic anhydride, 50 ℃ vacuum drying 10h.

The yield was 20.4 g, 91.6%.

To a 250mL triple-necked vial was added L-proline (9.8g, 1.3eq), sodium hydroxide (3.4g, 1.3eq), 100mL water, and 70mL tetrahydrofuran was dissolved by stirring at room temperature. Ice water bath cooled down to 0-10°C, dropwise addition of N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanine-N-carboxylic anhydride (20.0 g, 1.0eq) in 70 mL of tetrahydrofuran, dropwise addition was completed to control the temperature of 0-10 ℃ and continue to stir for 2h.

The pH was adjusted to 6 with hydrochloric acid and the tetrahydrofuran was evaporated under reduced pressure. The resulting aqueous solution with hydrochloric acid to adjust the pH to 4.2, extracted with ethyl acetate (200mL × 4), the organic phase concentrated under reduced pressure from the oil to 40mL ethyl acetate dissolved in 50 ℃ heating conditions dropwise addition of maleic acid (7.6g, 1.0eq) 180mL ethyl acetate solution, dropwise addition of the completion of the insulation to continue the reaction for 1h, naturally cooled down to 20 ～ 30 ℃, and continue to precipitate the crystals for 1h, and then filtered under reduced pressure to obtain the white solid maleic acid (7.6 g, 1.0 eq). Decompression filtration to obtain white solid enalapril maleate crude, washed with 40mL ethyl acetate, sample 50 ℃ vacuum drying 10h.

Record: 26.1g, yield 81.7%.

To 500mL three-necked bottle add 26.0g enalapril maleate crude, 200mL water, turn on the stirring, heating to 65 ℃, until the system dissolved clear continue to heat for 30min, turn off the heating, naturally fall to room temperature, there is white solid precipitation, ice water bath (0 ~ 10 ℃) continue to stir for 2h, filtration under reduced pressure, the cake was washed with 50mL of water, samples of 50 ℃ vacuum drying 10h to get the white Solid: 20.9g.

Yield: 80.6%, chromatographic purity: 99.90%.