Zofenopril Chemical Properties

Melting point:

129-131.5 °C(lit.)

alpha 

D25 -36.5° (c = 1 in methanol)

Boiling point:

646.3±55.0 °C(Predicted)

Density 

1.34±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: 5 mg/mL (11.64 mM)

pka

pK1:4.236 (25°C)

form 

crystalline

color 

light yellow

CAS DataBase Reference

81872-10-8(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn,Xi

Risk Statements 

22-37/38-41

Safety Statements 

23-24/25

WGK Germany 

3

RTECS 

QJ0875000

HazardClass 

IRRITANT

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

Zofenopril Usage And Synthesis

Originator

Zofenopril Calcium,ZYF Pharm Chemical

Uses

Zofenopril-d5 is intended for use as an internal standard for the quantification of Zofenopril by GC- or LC-mass spectrometry.

Definition

ChEBI: A proline derivative that is 4-(phenylsulfanyl)-L-proline in which the amine proton is replaced by a (2S)-3-(benzoylsulfanyl)-2-methylpropanoyl group. A prodrug for zofenoprilat.

Manufacturing Process

9.9 g (0.031 mole) of cis-4-phenylthio-L-proline is suspended in 100 ml of water (pH 5.6) and the pH is adjusted to 10.2 by the addition of about 20 ml of 10% sodium bicarbonate to provide a clear solution. The pH is then adjusted to 9.5 by the addition of about 4.5 ml of concentrated HCl. The solution is kept at 30°C while 8.1 g (0.033 mole) of (D)-3-(benzoylthio)-2- methylpropanoic acid chloride in 30 ml of toluene is added simultaneously with 100 ml of 10% sodium bicarbonate to keep the pH at 9.3. After about 1/4 of the acid chloride is added, a slimy precipitate begins to form which persists throughout the reaction. After stirring the reaction mixture at pH 9.3 for 2.5 h, it is made strongly acidic by adding 20% HCl in the presence of ethyl acetate. The aqueous layer is extracted twice with 350 ml portions of ethyl acetate and the combined organic layers are washed with 300 ml of saturated brine and dried (MgSO 4 ). The solvent is removed to yield 11.8 g of foamy solid cis-1-[D-3-(benzoylthyo)-2-methyl-1-oxopropyl]-4-(phenylthio)-L-proline hydrochloride.
To a solution of this cis-1-[D-3-(benzoylthyo)-2-methyl-1-oxopropyl]-4- (phenylthio)-L-proline hydrochloride 11.8 g (0.027 mole) in 70 ml of acetonitrile there is added about 6.0 g of dicyclohexylamine in 25 ml of ether. A white crystalline precipitate forms immediately. After standing overnight in the cold room, the solid is filtered and washed with ether to yield (cis)-1-[D- 3-(benzoylthio)-2-methyl-1-oxopropyl]-4-(phenylthio)-L-proline, dicyclohexylamine salt (1:1).
he slightly moist (cis)-1-[D-3-(benzoylthio)-2-methyl-1-oxopropyl]-4- (phenylthio)-L-proline dicyclohexylamine salt is stirred for 2.5 h in a mixture of 300 ml of ethyl acetate and 200 ml of 10% potassium bisulfate. Two clear layers form. The aqueous layer is extracted with two 200 ml portions of ethyl acetate and the combined organic layers are dried (MgSO 4 ). The solvent is removed to yield 10.1 g of foamy solid (cis)-1-[D-3-(benzoylthio)-2-methyl-1- oxopropyl]-4-(phenylthio)-L-proline; melting point 42-44°C.
In practice it is usually used as calcium salt (2:1).

brand name

Zoprace (Bristol-Myers Squibb).

Therapeutic Function

Antihypertensive

Synthesis Reference(s)

The Journal of Organic Chemistry, 33, p. 1675, 1968 DOI: 10.1021/jo01268a091

Zofenopril(81872-10-8)Related Product Information

• 1-Triacontanol
• Gibberellic acid
• Chlormequat chloride
• Potassium Phosphate Monobasic
• Carbendazim
• Paclobutrazol
• Uniconazole
• Abscisic acid
• 1-Naphthaleneacetic acid
• Zofenoprilat
• Zofenopril calcium
• (2S)-1-(3-Acetylthio-2-methyl-1-oxopropyl)-L-proline
• Captopril
• Zofenopril
• D-(S)-3-acetylthio-2-methylpropionylL-proline
• CHEMBRDG-BB 9071613
• 4-PHENYLSULFANYL-BUTYRIC ACID
• N-(3-MERCAPTO-2-METHYLPROPANOYL)GLYCINE