85441-61-8

Basic information

• Product Name: Quinapril
• Synonyms: QUINAPRIL HCL;PD-109452-2;CI-906;(3S)-2-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-Isoquinolinecarboxylic acid;(S)-2-((S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)aMino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;(3s-(2(r*(r*)),3r*))-2-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride;(3S)-2-[(2S)-2-[[(1S)-1-(ETHOXYCARBONYL)-3-PHENYLPROPYL]AMINO]-1-OXOPROPYL]-1,2,3,4-TETRAHYDRO-3-ISOQUINOLINECARBOXYLIC ACID HYDROCHLORIDE;ACCUPRIL
• CAS NO: 85441-61-8
• Molecular Formula: C₂₅H₃₀N₂O₅
• Molecular Weight: 438.52
• EINECS: 1312995-182-4
• Mol File: 85441-61-8.mol
• Article Data: 6

Chemical Properties

• Melting Point: 120-130°C
• Boiling Point: 662 °C at 760 mmHg
• Flash Point: 354.1 °C
• Appearance: /
• Density: 1.217 g/cm³
• PKA: 3.39±0.20(Predicted)
• CAS DataBase Reference: Quinapril(CAS DataBase Reference)
• NIST Chemistry Reference: Quinapril(85441-61-8)
• EPA Substance Registry System: Quinapril(85441-61-8)

Safety Data

• Safety Statements: 22-24/25
• Hazardous Substances Data: 85441-61-8(Hazardous Substances Data)

Usage

Description

Quinapril is an orally active, non-sulfhydryl ACE inhibitor reportedly useful in the treatment of essential hypertension. The main claimed advantage of quinapril compared with other available ACE inhibitors is its side-effect profile. It is also effective in the management of congestive heart failure.

Brand name

Accupril (Pfizer); Quinapril (Lupin); Quinapril (Ranbaxy) ;Accupro.

Clinical Use

Angiotensin converting enzyme inhibitor: Hypertension Congestive heart failure

Metabolism

Quniapril is a prodrug which is metabolised in the liver to its active form, quinaprilat, and to minor inactive metabolites. Quinaprilat is eliminated primarily by renal excretion.

InChI:InChI=1/C25H30N2O5/c1-3-32-25(31)21(14-13-18-9-5-4-6-10-18)26-17(2)23(28)27-16-20-12-8-7-11-19(20)15-22(27)24(29)30/h4-12,17,21-22,26H,3,13-16H2,1-2H3,(H,29,30)/t17-,21-,22-/m0/s1

Synthetic route

L-Tic-OH (74163-81-8) + N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanine (877932-98-4) + L-alanine acid chloride (129178-93-4) → quinapril (85441-61-8)

Conditions	Yield
With benzenesulfonamide; phosphorus pentachloride; triethylamine In n-heptane; dichloromethane; water	83.9%

tert-butyl (S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)-L-alanyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (82586-56-9) → quinapril (85441-61-8)

Conditions	Yield
With trifluoroacetic acid for 1h; Ambient temperature;

quinapril hydrochloride (82586-55-8) → quinapril (85441-61-8) + <3S-<2(R*),3α,11aβ>>-1,3,4,6,11,11a-hexahydro-3-methyl-1,4-dioxo-α-(2-phenylethyl)-2H-pyrazino<1,2-b>isoquinoline-2-acetic acid, ethyl ester (103733-49-9)

Conditions	Yield
With citric acid at 80℃; pH=2.60; Kinetics; Further Variations:; pH-values;

quinapril benzyl ester (82586-54-7) → quinapril (85441-61-8)

Conditions	Yield
With hydrogen; palladium on activated charcoal
With hydrogenchloride; hydrogen; 5%-palladium/activated carbon In water; acetone at 35 - 40℃; under 367.786 Torr; for 5h; Product distribution / selectivity;

[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine (82717-96-2) → quinapril (85441-61-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triphenylphosphine / CH2Cl2 / 0.75 h 1.2: 45 percent / CH2Cl2 / 2.5 h / 25 - 30 °C 2.1: triethylamine / CH2Cl2 / 4 h / -15 - -10 °C 3.1: hydrogen / Pd/C View Scheme

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine-2'-benzothiazolylthio ester (124492-03-1) → quinapril (85441-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / CH2Cl2 / 4 h / -15 - -10 °C 2: hydrogen / Pd/C View Scheme

L-Tic-OH (74163-81-8) → quinapril (85441-61-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2SO4 / dioxane / 17 h / Ambient temperature 2: 78 percent / Et3N, DCC, 1-hydroxybenzotriazole / tetrahydrofuran / Ambient temperature 3: TFA / 1 h / Ambient temperature View Scheme

(S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester (77497-74-6) → quinapril (85441-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / Et3N, DCC, 1-hydroxybenzotriazole / tetrahydrofuran / Ambient temperature 2: TFA / 1 h / Ambient temperature View Scheme

N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine hydrochloride (80828-26-8) → quinapril (85441-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / Et3N, DCC, 1-hydroxybenzotriazole / tetrahydrofuran / Ambient temperature 2: TFA / 1 h / Ambient temperature View Scheme

C33H38N2O5 → quinapril (85441-61-8)

Conditions	Yield
With hydrogenchloride; hydrogen; 5%-palladium/activated carbon In ethanol; water at 35 - 40℃; under 367.786 Torr; for 5h; Product distribution / selectivity;

quinapril (85441-61-8) → <3S-<2(R*),3α,11aβ>>-1,3,4,6,11,11a-hexahydro-3-methyl-1,4-dioxo-α-(2-phenylethyl)-2H-pyrazino<1,2-b>isoquinoline-2-acetic acid, ethyl ester (103733-49-9)

Conditions	Yield
With acetic acid In toluene at 95℃; for 0.5h;	80%

quinapril (85441-61-8) → ethanol (64-17-5) + quinaprilate (82768-85-2)

Conditions	Yield
With Tris-HCl buffer; human liver carboxylesterase pI 4.5 at 37℃; pH=7.4; Enzyme kinetics; Further Variations:; Reagents; Hydrolysis;

Upstream product

• 74163-81-8 L-Tic-OH 
• 877932-98-4 N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanine 
• 129178-93-4 L-alanine acid chloride 
• 124492-03-1 N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine-2'-benzothiazolylthio ester 
• 82717-96-2 [1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine 
• 82586-54-7 quinapril benzyl ester 
• 82586-55-8 quinapril hydrochloride 
• 82586-56-9 tert-butyl (S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)-L-alanyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 
• 80828-26-8 N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine hydrochloride 
• 77497-74-6 (S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester 

Downstream Products

• 64-17-5 ethanol 
• 82768-85-2 quinaprilate 
• 103733-49-9 <3S-<2(R*),3α,11aβ>>-1,3,4,6,11,11a-hexahydro-3-methyl-1,4-dioxo-α-(2-phenylethyl)-2H-pyrazino<1,2-b>isoquinoline-2-acetic acid, ethyl ester 

Relevant articles and documents

COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE

To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.

2′-Benzothiazolylthioesters of N-substituted alpha amino acids: Versatile intermediates for synthesis of ACE inhibitors

ACE inhibitors have been synthesized from novel active esters using simple reaction conditions in high diastereomeric selectivity. The active esters may be obtained from the corresponding carboxylic acids or their acid chlorides.

Process for preparing an angiotensin converting enzyme inhibitor

-