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Ramipril

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Name

Ramipril

EINECS 642-904-3
CAS No. 87333-19-5 Density 1.2 g/cm3
PSA 95.94000 LogP 2.71200
Solubility N/A Melting Point 106-108 °C
Formula C23H32N2O5 Boiling Point 616.2 °C at 760 mmHg
Molecular Weight 416.517 Flash Point 326.4 °C
Transport Information N/A Appearance White solid
Safety 26-37/39 Risk Codes 36/38
Molecular Structure Molecular Structure of 87333-19-5 (Ramipril) Hazard Symbols IrritantXi
Synonyms

Altace;Hytren;Carasel;Cardace;Vesdil;Pramace;Cyclopenta(b)pyrrole-2-carboxylic acid, 1-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydro-, (2S-(1(R*(R*)),2alpha,3abeta,6abeta))-;Quark;HOE 498;Triatec;Acovil;(2S-(1(R*(R*)),2alpha,3abeta,6abeta))-1-(2-((1-(Ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydrocyclopenta(b)pyrrole-2-carboxylic acid.;

Article Data 20

Ramipril Synthetic route

87269-88-3

2--L-alanyl>-(1S,3S,5S)-2-azabicyclo<3.3.0>octane-3-carboxylic acid benzylester

87333-19-5

Ramipril

Conditions
ConditionsYield
With hydrogen; palladium on activated charcoal In ethanol at 0 - 10℃; under 1838.94 - 2206.73 Torr;95%
With hydrogen; palladium 10% on activated carbon In methanol at 20℃; under 760.051 Torr; for 1.5h; Product distribution / selectivity;80%
With hydrogen; 3% Pd/C In ethanol at 20 - 25℃; under 760.051 Torr; for 1 - 3h; Product distribution / selectivity;78%

(2S,3aS,6aS)-1-[(S)-2-[[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-amino]propanoyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid monohydrate

87333-19-5

Ramipril

Conditions
ConditionsYield
at 40℃; under 2 Torr; for 10 - 12h; Product distribution / selectivity;94%
114192-42-6

N-[(S)-1-carbethoxy-3-phenyl-propyl]-S-alaninoyl chloride hydrochloride

109428-53-7

(2S,3aS,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid

87333-19-5

Ramipril

Conditions
ConditionsYield
Stage #1: (2S,3aS,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid With sodium ethanolate; triethylamine In ethanol at -40℃;
Stage #2: N-[(S)-1-carbethoxy-3-phenyl-propyl]-S-alaninoyl chloride hydrochloride In ethanol; dichloromethane at -50 - 20℃; for 1.08333h;
Stage #3: With hydrogenchloride In water pH=4.2; Acidic aqueous solution;
88%

C8H13NO2*(x)ClH

84793-24-8

N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride

87333-19-5

Ramipril

Conditions
ConditionsYield
With sodium hydroxide In water at 10 - 15℃; pH=8.5 - 9.5;74%
87269-87-2, 87679-25-2, 88547-79-9, 93779-29-4, 94569-19-4, 138877-09-5

benzyl (2S,3AS,6AS)-octahydrocyclopenta[b]pyrrole-2-carboxylate hydrochloride

84793-24-8

N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride

87333-19-5

Ramipril

Conditions
ConditionsYield
With acetic acid; triethylamine In ethyl acetate at 5 - 20℃; for 4h;74%
82717-96-2

[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine

87333-19-5

Ramipril

Conditions
ConditionsYield
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
124492-03-1

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine-2'-benzothiazolylthio ester

87333-19-5

Ramipril

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: triethylamine / CH2Cl2 / 4 h / -15 - -10 °C
2: hydrogen / Pd/C
View Scheme
15121-89-8

ethyl (E)-4-oxo-4-phenyl-2-butenoate

87333-19-5

Ramipril

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 1.) 2N NaOH, 2.) N(C2H5)3 / 1.) methylene chloride, 2.) ethanol, 2 h
2: 90 percent / H2, 1.6percent H2SO4 / 10percent Pd/C / acetic acid / 7 h / 30002.4 Torr / Ambient temperature
3: 95 percent / K2CO3, 25percent ethylmethylphosphinic anhydride / H2O; CH2Cl2
4: H2 / 10percent Pd/C / methanol / 0.5 h / 750.06 - 3750.3 Torr / Ambient temperature
View Scheme
87269-87-2, 87679-25-2, 88547-79-9, 93779-29-4, 94569-19-4, 138877-09-5

benzyl (2S,3AS,6AS)-octahydrocyclopenta[b]pyrrole-2-carboxylate hydrochloride

87333-19-5

Ramipril

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 95 percent / K2CO3, 25percent ethylmethylphosphinic anhydride / H2O; CH2Cl2
2: H2 / 10percent Pd/C / methanol / 0.5 h / 750.06 - 3750.3 Torr / Ambient temperature
View Scheme
87269-87-2, 87679-25-2, 88547-79-9, 93779-29-4, 94569-19-4, 138877-09-5

(1RS,3RS,5RS)-2-Azabicyclo<3.3.0>octan-3-carbonsaeurebenzylester-hydrochlorid

87333-19-5

Ramipril

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 67.8 g / 1.) 10percent NaOH 2.) 6N HCl / CH2Cl2; ethyl acetate
2: 95 percent / K2CO3, 25percent ethylmethylphosphinic anhydride / H2O; CH2Cl2
3: H2 / 10percent Pd/C / methanol / 0.5 h / 750.06 - 3750.3 Torr / Ambient temperature
View Scheme

Ramipril Specification

The IUPAC name of Ramipril is (2S,3aS,6aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrole-2-carboxylic acid. With the CAS registry number 87333-19-5, it is also named as Cyclopenta(b)pyrrole-2-carboxylic acid, 1-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydro-, (2S-(1(R*(R*)),2alpha,3abeta,6abeta))-; Lostapres. The product's categories are active pharmaceutical ingredients, ramipril, aromatics, heterocycles, intermediates & fine chemicals, pharmaceuticals and angiotensin. It is white solid.

The other characteristics of this product can be summarized as: (1)ACD/LogP: 3.41; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 1.24; (4)ACD/BCF (pH 5.5): 1.57; (5)ACD/BCF (pH 7.4): 1; (6)ACD/KOC (pH 5.5): 11.66; (7)ACD/KOC (pH 7.4): 1; (8)#H bond acceptors: 7; (9)#H bond donors: 2; (10)#Freely Rotating Bonds: 10; (11)Index of Refraction: 1.555; (12)Molar Refractivity: 111.41 cm3; (13)Molar Volume: 346.8 cm3; (14)Polarizability: 44.16×10-24 cm3; (15)Surface Tension: 50.1 dyne/cm; (16)Enthalpy of Vaporization: 96.09 kJ/mol; (17)Vapour Pressure: 4.86E-16 mmHg at 25°C; (18)Rotatable Bond Count: 10; (19)Exact Mass: 416.231122; (20)MonoIsotopic Mass: 416.231122; (21)Topological Polar Surface Area: 95.9; (22)Heavy Atom Count: 30.

Uses of Ramipril: It is an angiotensin-converting enzyme (ACE) inhibitor which is used to treat hypertension and congestive heart failure. ACE inhibitors lower the production of angiotensin II, therefore relaxing arterial muscles while at the same time enlarging the arteries, allowing the heart to pump blood more easily, and increasing blood flow due to more blood being pumped into and through larger passageways.

When you are using this chemical, please be cautious about it as the following: 
It is irritating to eyes and skin. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. If you want to contact this product, you must wear suitable gloves and eye/face protection.

People can use the following data to convert to the molecule structure.
1. SMILES: O=C(OCC)[C@@H](N[C@H](C(=O)N1[C@H](C(=O)O)C[C@@H]2CCC[C@H]12)C)CCc3ccccc3;
2. InChI: InChI=1/C23H32N2O5/c1-3-30-23(29)18(13-12-16-8-5-4-6-9-16)24-15(2)21(26)25-19-11-7-10-17(19)14-20(25)22(27)28/h4-6,8-9,15,17-20,24H,3,7,10-14H2,1-2H3,(H,27,28)/t15-,17-,18-,19-,20-/m0/s1.

The following is the toxicity data which has been tested.

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD50 intravenous > 250mg/kg (250mg/kg)   New Cardiovascular Drugs. Vol. 5, Pg. 57, 1987.
dog LD50 oral > 1gm/kg (1000mg/kg)   Arzneimittel-Forschung. Drug Research. Vol. 38, Pg. 14, 1988.
mouse LD50 intravenous 1100mg/kg (1100mg/kg)   New Cardiovascular Drugs. Vol. 5, Pg. 57, 1987.
mouse LD50 oral 10048mg/kg (10048mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

LUNGS, THORAX, OR RESPIRATION: DYSPNEA
Arzneimittel-Forschung. Drug Research. Vol. 38, Pg. 14, 1988.
 
rat LD50 intravenous 600mg/kg (600mg/kg)   New Cardiovascular Drugs. Vol. 5, Pg. 57, 1987.
rat LD50 oral > 10gm/kg (10000mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY) Arzneimittel-Forschung. Drug Research. Vol. 38, Pg. 14, 1988.
 

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