104713-75-9

Basic information

• Product Name: (+)-(3'S,4S)-1-Benzyl-3-pyrrolidinyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
• Synonyms: BARNIDIPINE;(+)-(3'S,4S)-1-Benzyl-3-pyrrolidinyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate;(4S)-1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-methyl 5-[(3S)-1-benzylpyrrolidin-3β-yl] ester;(4S)-1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 5-methyl 3-[(3S)-1-benzylpyrrolidin-3-yl] ester;(4S)-2,6-Dimethyl-1,4-dihydro-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 5-methyl 3-[(3S)-1-benzylpyrrolidin-3-yl] ester;(S)-3-((S)-1-Benzylpyrrolidin-3-yl) 5-Methyl 2,6-diMethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;(S)-3-((S)-1-Benzylpyrrolidin-3-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3;(S)-3-((S)-1-Benzylpyrrolidin-3-yl)-5-methyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridin
• CAS NO: 104713-75-9
• Molecular Formula: C₂₇H₂₉N₃O₆
• Molecular Weight: 491.54
• Mol File: 104713-75-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 137-139°
• Boiling Point: 614.5 °C at 760 mmHg
• Flash Point: 325.4 °C
• Appearance: /
• Density: 1.31 g/cm³
• Vapor Pressure: 4.94E-15mmHg at 25°C
• Refractive Index: 1.628
• Storage Temp.: 2-8°C
• PKA: 7.62±0.40(Predicted)
• CAS DataBase Reference: (+)-(3'S,4S)-1-Benzyl-3-pyrrolidinyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-(3'S,4S)-1-Benzyl-3-pyrrolidinyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate(104713-75-9)
• EPA Substance Registry System: (+)-(3'S,4S)-1-Benzyl-3-pyrrolidinyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate(104713-75-9)

Safety Data

• Hazardous Substances Data: 104713-75-9(Hazardous Substances Data)

Usage

Originator

Barnidipine,Yamanouchi

Manufacturing Process

In 5 ml of isopropyl alcohol were dissolved 1.5 g (0.01 mole) of 3- nitrobenzaldehyde, 2.6 g (0.01 mole) of 1-benzyl-3-acetoacetyloxypyrrolidine, and 1.3 g (0.01 mole) of β-aminocrotonic acid methyl ester and then the solution was refluxed for 8 hours. The solvent was distilled off under reduced pressure, the residue obtained was dissolved in a small amount of chloroform, and the solution was applied to silica gel column chromatography (column diameter 1.5 cm, height 20 cm, and about 200 ml of chloroform was used as the eluent). The eluates were collected and concentrated to give 3.4 g of oily 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3- (1-benzylpyrrolidin-3-yl)ester-5-methyl ester: [α]D 20=+64.8° (c = 1 in methanol).

Therapeutic Function

Coronary vasodilator

InChI:InChI=1/C27H29N3O6/c1-17-23(26(31)35-3)25(20-10-7-11-21(14-20)30(33)34)24(18(2)28-17)27(32)36-22-12-13-29(16-22)15-19-8-5-4-6-9-19/h4-11,14,22,25,28H,12-13,15-16H2,1-3H3/t22-,25-/m0/s1

Upstream product

• 76093-33-9 (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 101385-90-4 (S)-N-benzyl-3-hydroxypyrrolidine 
• 74936-72-4 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 75130-24-4 2,6-dimethyl-4-(3-nitrophenyl)-5-methoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid 2-cyanoethyl ester 
• 102993-38-4 2-cyanoethyl 2-(3-nitrobenzylidene)-3-oxobutanoate 
• 88712-56-5 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-5-carboxylic acid chloride 
• 14205-39-1 methyl 3-aminocrotonate 
• 100-46-9 benzylamine 
• 775-15-5 1-benzyl-3-pyrrolidinol 
• 71863-55-3 (+/-)-1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 99-61-6 3-nitro-benzaldehyde 
• 101930-02-3 (3RS)-1-benzyl-3-pyrrolidinyl methyl (4RS)2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride 
• 101930-01-2 (S)-3-acetoacetoxy-1-benzylpyrrolidine 
• 101469-91-4 (3S)-1-benzyl-3-hydroxypyrrolidine-2,5-dione 

Downstream Products

• 172331-68-9 3-(R)-1-benzylpyrrolidin-3-yl 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate 
• 104757-53-1 [14C]-Barnidipine hydrochloride 
• 172331-68-9 2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-((S)-1-benzyl-pyrrolidin-3-yl) ester 5-methyl ester 

Relevant articles and documents

Process for synthesis of hydrochloric acid ramiah of lercanidipine (by machine translation)

The invention discloses a process for synthesizing hydrochloric acid ramiah of lercanidipine, its synthesis process comprises the following steps : (1) 3 -? Hydroxy-propionitrile (I) and (II) reaction of ketene dimer, to obtain compound (VI) ; (2) compound (III) with (VI) reaction between formaldehyde nitrobenzene, to obtain compound (VII) ; (3) compound (VII) with β-amino-crotonic acid ethyl ester (IV) reaction, to obtain compound (VIII) ; (4) by strong alkali hydrolysis of compound (VIII), to obtain compound (IX) ; (5) compound (IX) using chiral organic alkali splitting, to obtain compound (X) ;? (6) compound (X) with benzyl quick (V) reaction, to obtain compound (XI) ; (7) a solution of compound (XI) by adding hydrogen chloride, hydrochloric acid ramiah horizontal (XII) can be obtained. Synthetic process of this invention has the following several advantages : (1) mild reaction conditions, each step the product is easy to separate, purification, controllable quality ; (2) higher yield for each step, the used original helping material is easy to obtain, the total cost is low ; (3) do not need to be too column, is suitable for industrial production. (by machine translation)

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

Stereoselectivity of a Potent Calcium Antagonist, 1-Benzyl-3-pyrrolidinyl Methyl 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated.The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a*HBr as well as 3a*HCl.The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation.The potency order of the four enantiomers was (S,S)-3a > (S,R)-3b > (R,R)-3d > (R,S)-3c.Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a*HCl or 3a*HBr.On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5.The conformational restriction may be a factor causing stereoselectivity of antagonism.