39562-70-4

Basic information

• Product Name: Nitrendipine
• Synonyms: NITRENDIPINE;1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylicacidethy;baye5009;bayotensin;baypress;ethylmethyl1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxy;lmethylester;nidrel
• CAS NO: 39562-70-4
• Molecular Formula: C₁₈H₂₀N₂O₆
• Molecular Weight: 360.36
• EINECS: 254-513-1
• Product Categories: Pharmaceutical;Intermediates & Fine Chemicals;Pharmaceuticals;Calcium channel;Ion Channels;API;Pharmaceutical intermediate;Pharmaceutical intermediates
• Mol File: 39562-70-4.mol
• Article Data: 27

Chemical Properties

• Melting Point: 1580C
• Boiling Point: 492.4°C (rough estimate)
• Flash Point: 249.5 °C
• Appearance: yellow to green/powder
• Density: 1.3595 (rough estimate)
• Vapor Pressure: 8.08E-09mmHg at 25°C
• Refractive Index: 1.5700 (estimate)
• Storage Temp.: Store at RT
• Solubility: methanol: 15 mg/mL
• PKA: 2.79±0.70(Predicted)
• Water Solubility: Soluble in DMSO (17.5 mg/ml), methanol (15 mg/ml), ethyl acetate, and ethanol (25 mM). Insoluble in water.
• Stability: Stable for 1 year from date of purchase as supplied. Protect from light. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 week.
• CAS DataBase Reference: Nitrendipine(CAS DataBase Reference)
• NIST Chemistry Reference: Nitrendipine(39562-70-4)
• EPA Substance Registry System: Nitrendipine(39562-70-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• WGK Germany: 1
• RTECS: US5653000
• Hazardous Substances Data: 39562-70-4(Hazardous Substances Data)

Usage

Description

Nitrendipine is a vasodilating, dihydropyridine calcium antagonist. Its prolonged therapeutic effect in comparison to nifedipine makes it useful in the once to twice daily treatment of hypertension.

Chemical Properties

Crystalline Solid

Originator

Bayer (W. Germany)

Uses

Different sources of media describe the Uses of 39562-70-4 differently. You can refer to the following data:
1. Nitrendipine modulates NMDA receptor channel function in mammalian neurons. Nitrendipine has been shown to inhibit neutrophil adhesion to vascular endothelium. It is used in the treatment of primary hypertension to decrease blood pressure. Nitrendipine is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina.
2. Antihypertensive;Calcium channel blocker
3. Nitrendipine is a dihydropyridine calcium channel blocker. Nitrendipine is used in the treatment of primary (essential) hypertension to decrease blood pressure. Antihypertensive.

Definition

ChEBI: A dihydropyridine that is 1,4-dihydropyridine substituted by methyl groups at positions 2 and 6, a 3-nitrophenyl group at position 4, a ethoxycarbonyl group at position 3 and a methoxycarbonyl group at position 5. It is a calcium-channel blocker used in t e treatment of hypertension.

Brand name

Baypress (Bayer);BAYOTENSIN.

General Description

Nitrendipine, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylic acid methyl ethylester (Baypress), is a second-generation dihydropyridinechannel blocker of the nifedipine type. It is more selectivefor vascular smooth muscle than for myocardial tissue andserves as an effective vasodilator. The drug is used in thetreatment of mild-to-moderate essential hypertension.

Biochem/physiol Actions

Ca2+ channel blocker; anti-hypertensive.

References

1) Meyer et al., (1981), (Synthesis and comparative pharmacological studies of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylates with non-identical ester functions); Arzneimittelforschung 31 407 2) Stoepel et al., (1981), Pharmacological studies of the antihypertensive effect of nitrendipine; Arzneimittelforschung 31 2056

InChI:InChI=1/C18H20N2O6/c1-5-26-18(22)15-11(3)19-10(2)14(17(21)25-4)16(15)12-7-6-8-13(9-12)20(23)24/h6-9,15-16H,5H2,1-4H3/t15?,16-/m1/s1

Synthetic route

ethyl acetoacetate (141-97-9) + 3-nitro-benzaldehyde (99-61-6) + methyl 3-aminocrotonate (14205-39-1) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With sodium tosylate In water for 0.4h; Reagent/catalyst; Time; Hantzsch Dihydropyridine Synthesis; Microwave irradiation; Reflux; Green chemistry;	94%
With C21H38N(1+)*Mo11O40PV(4-)*3H(1+) In ethanol at 78℃; for 8h; Catalytic behavior; Hantzsch Pyridine Synthesis; Green chemistry;	78%
Hantzsch Dihydropyridine Synthesis; Darkness; Reflux;	59%

Benzyl-{2-[5-methoxycarbonyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carbonyloxy]-ethyl}-dimethyl-ammonium; iodide → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With potassium hydroxide In ethanol at 25℃;	92%

(S)-1,1-Dibenzyl-3-[(R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carbonyloxy]-piperidinium; bromide → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With potassium hydroxide In ethanol at 25℃; for 24h;	92%
Multi-step reaction with 3 steps 1: 67 percent / KOH / tetrahydrofuran / 24 h / 25 °C 2: 93 percent / acetone / Heating 3: 92 percent / KOH / ethanol / 25 °C View Scheme

methanol (67-56-1) + C23H27N4O6(1+)*F6P(1-) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With sodium methylate for 16h; Reflux;	92%

(S)-1-Benzyl-3-[(R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carbonyloxy]-1-methyl-piperidinium; iodide → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With potassium hydroxide In ethanol at 25℃;	91%
Multi-step reaction with 3 steps 1: 32 percent / KOH / tetrahydrofuran / 25 °C 2: 93 percent / acetone / Heating 3: 92 percent / KOH / ethanol / 25 °C View Scheme

ethyl aminocrotonate + methyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate (119128-13-1) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In isopropyl alcohol for 10h; Heating / reflux;	89%

methyl 2-(3-nitrophenylmethylene)acetoacetate (39562-17-9) + ethyl aminocrotonate (626-34-6, 7318-00-5, 41867-20-3) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In ethanol for 6h; Reflux;	86%
at 90℃; for 0.15h; Microwave irradiation;

methyl 3-aminocrotonate (21731-17-9) + ethyl 2-[(3-Nitrophenyl)methylene]-3-oxobutanoate (39562-16-8) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Stage #1: methyl 3-aminocrotonate; ethyl 2-[(3-Nitrophenyl)methylene]-3-oxobutanoate In ethanol at 75 - 80℃; for 1h; Stage #2: With acetic anhydride In ethanol at 75 - 80℃; for 1h; Solvent;	86%

(S)-1-Allyl-1-benzyl-3-[(R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carbonyloxy]-piperidinium; bromide → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With potassium hydroxide In ethanol at 25℃;	85%
Multi-step reaction with 3 steps 1: 26 percent / KOH / tetrahydrofuran / 25 °C 2: 93 percent / acetone / Heating 3: 92 percent / KOH / ethanol / 25 °C View Scheme

ethyl 2-(3-nitrophenylmethylene)-3-oxobutanoate (39562-16-8) + methyl 3-aminocrotonate (14205-39-1) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Stage #1: ethyl 2-(3-nitrophenylmethylene)-3-oxobutanoate; methyl 3-aminocrotonate In ethanol at 70 - 75℃; for 1h; Stage #2: With hydrogenchloride In ethanol; water at 70 - 75℃;	80%
In ethanol for 8h; Heating;	79%
With acetic acid; N-ethyl-N,N-diisopropylamine In ethanol Reflux;

ethyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate (39562-16-8) + 1,1,1-Triphenyl-3-methyl-4-(methoxycarbonyl)-2-aza-1λ5-phosphabuta-1,3-diene (81777-30-2) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In chloroform at 25℃; for 0.5h;	77%

ethyl acetoacetate (141-97-9) + 3-nitro-benzaldehyde (99-61-6) + methyl (E)-3-aminocrotonate (14205-39-1) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With sodium butylmonoglycolsulphate In water for 0.0833333h; Heating; Irradiation; microwave irradiation;	72%

3'-nitrobenzylideneacetoacetic acid ethyl ester (70076-42-5) + methyl 3-aminocrotonate (21731-17-9) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In ethanol	67%

ethyl acetoacetate (141-97-9) + 3-nitro-benzaldehyde (99-61-6) + acetoacetic acid methyl ester (105-45-3) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With aluminum oxide; ammonia In methanol Hantzsch pyridine synthesis; Heating;	50%
With pyridine; 4 A molecular sieve; polysterene-based acid-cleavable Rink amine resin; trifluoroacetic acid 1) CH2Cl2, rt, 3 d; 2) 45 deg C, 24 h; 3) CH2Cl2, 45 min;; Yield given. Multistep reaction;

methyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate (119128-13-1) + ethyl acetoacetate (141-97-9) → m-nifedipine (21881-77-6) + 2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester (21829-28-7) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With ammonium hydroxide In ethanol for 24h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethyl acetoacetate (141-97-9) + 3-nitro-benzaldehyde (99-61-6) + methyl (E)-3-aminocrotonate (14205-39-1) → m-nifedipine (21881-77-6) + 2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester (21829-28-7) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In ethanol for 10h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

3-nitro-benzaldehyde (99-61-6) + ethyl (E)-3-aminobut-2-enoate (41867-20-3) + acetoacetic acid methyl ester (105-45-3) → m-nifedipine (21881-77-6) + 2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester (21829-28-7) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
In ethanol for 10h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate (39562-16-8) + acetoacetic acid methyl ester (105-45-3) → m-nifedipine (21881-77-6) + 2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester (21829-28-7) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With ammonium hydroxide In ethanol for 24h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

Nicardipine (55985-32-5) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / acetone / Heating 2: 92 percent / KOH / ethanol / 25 °C View Scheme

(R)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((S)-1-benzyl-piperidin-3-yl) ester 5-methyl ester → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / CHCl3 / Heating 2: 67 percent / KOH / tetrahydrofuran / 24 h / 25 °C 3: 93 percent / acetone / Heating 4: 92 percent / KOH / ethanol / 25 °C View Scheme
Multi-step reaction with 2 steps 1: 93 percent / CHCl3 / Heating 2: 92 percent / KOH / ethanol / 24 h / 25 °C View Scheme
Multi-step reaction with 4 steps 1: 95 percent / CHCl3 / Heating 2: 26 percent / KOH / tetrahydrofuran / 25 °C 3: 93 percent / acetone / Heating 4: 92 percent / KOH / ethanol / 25 °C View Scheme

3-nitro-benzaldehyde (99-61-6) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: gaseous HCl / toluene / 40 h / Ambient temperature 2: 79 percent / ethanol / 8 h / Heating View Scheme
Multi-step reaction with 2 steps 1: piperidine; acetic acid / 30 °C / Neat (no solvent) 2: ethanol / 6 h / Reflux View Scheme

acetoacetic acid methyl ester (105-45-3) + n-C7H15Br or n-C7H15I → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: gaseous NH3, p-toluenesulfonic acid / toluene / Heating 2: 79 percent / ethanol / 8 h / Heating View Scheme

(+)-2-methylthiomethyl-6-methyl-5-carbomethoxy-3-carboethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine (131767-68-5, 131796-79-7) + methyl iodide (74-88-4) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With sodium borohydrid In N,N-dimethyl-formamide

methyl (S)-3-[(2-methoxy-methylpyrrolidin-1-yl)-imino]-butyrate + 2,3-dimethyl-2,3-diaminobutane (20485-44-3) + ethyl 2-[(3-Nitrophenyl)methylene]-3-oxobutanoate (39562-16-8) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
With n-butyllithium; ammonium chloride In tetrahydrofuran; methanol; hexane; dichloromethane

acetoacetic acid methyl ester (105-45-3) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: piperidine; acetic acid / 30 °C / Neat (no solvent) 2: ethanol / 6 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: ammonia / ethanol / 4 h / 2 - 20 °C 2: acetic acid; N-ethyl-N,N-diisopropylamine / ethanol / Reflux View Scheme

3-nitro-benzaldehyde (99-61-6) + acetoacetic acid methyl ester (105-45-3) → 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: alumina / neat (no solvent) / 120 °C / Microwave irradiation; Green chemistry 2: 0.15 h / 90 °C / Microwave irradiation View Scheme

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → (+/-)-Oxidized Nitrendipine (89267-41-4)

Conditions	Yield
With ammonium cerium(IV) nitrate In water; acetone for 0.166667h; Ambient temperature;	100%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; iron(III) chloride hexahydrate; oxygen; sodium nitrite In acetic acid; acetonitrile at 20℃; for 0.75h;	97%
With lead(IV) acetate In dichloromethane; acetic acid at 20℃; for 1.25h;	96%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) + methyl iodide (74-88-4) → N-methylnitrendipine (50698-12-9)

Conditions	Yield
	95%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) + phenylboronic acid (98-80-6) → 3-ethyl 5-methyl 2,6-dimethyl-4-(3-(phenylsulfonamido)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Conditions	Yield
With potassium pyrosulfite; tetrabutyl-ammonium chloride; potassium carbonate In acetonitrile at 130℃; for 24h; Sealed tube;	61%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → N-nitroso-nitrendipine

Conditions	Yield
With hydrogenchloride; sodium nitrite In water at 37℃; for 6h; pH=3 - 3.5;	44%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) + allyl bromide (106-95-6) → 1-allyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester

Conditions	Yield
	22%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) + propargyl bromide (106-96-7) → MRS 1845

Conditions	Yield
	22%

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) + ethyl iodide (75-03-6) → 1-ethyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester

Conditions	Yield
	21%

benzyl chloride (100-44-7) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → 1-benzyl-2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl ester 5-ethyl ester

Conditions	Yield
	16%

1H-imidazole (288-32-4) + 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → 1,4-dihydro-2,6-bis(1H-imidazol-1-ylmethyl)-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid ethyl methyl diester (123754-04-1)

Conditions	Yield
With phenyltrimethylammonium tribromide 1.) MeCN, below 10 deg C, 0.75 h, 2.) below 30 deg C, 2 h; Yield given. Multistep reaction;

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → SL 5721 (64603-72-1) + 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (74936-72-4) + methyl 2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydro-furo<3,4-b>pyridine-3-carboxylate (64603-74-3) + ethyl-2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydrofuro<3,4-b>3-pyridinecarboxylate (89288-25-5) + (R)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl) ester 5-methyl ester (138135-46-3) + (S)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl) ester 5-methyl ester (138135-45-2)

Conditions	Yield
biotransformation in rat, dog, and mouse (in vivo and in vitro);

1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester (39562-70-4) → 2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester; compound with nitric acid

Conditions	Yield
With nitric acid for 4h; Heating;

Upstream product

• 141-97-9 ethyl acetoacetate 
• 99-61-6 3-nitro-benzaldehyde 
• 105-45-3 acetoacetic acid methyl ester 
• 20485-44-3 2,3-dimethyl-2,3-diaminobutane 
• 39562-16-8 ethyl 2-[(3-Nitrophenyl)methylene]-3-oxobutanoate 
• 70076-42-5 3-nitrobenzylidene acetoacetic acid ethyl ester 
• 21731-17-9 methyl 3-aminocrotonate 
• 131767-68-5 (+)-2-methylthiomethyl-6-methyl-5-carbomethoxy-3-carboethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine 
• 74-88-4 methyl iodide 
• 119128-13-1 methyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate 
• 119065-61-1 (R)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((S)-1-benzyl-piperidin-3-yl) ester 5-methyl ester 
• 55985-32-5 Nicardipine 
• 39562-16-8 ethyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate 
• 81777-30-2 1,1,1-Triphenyl-3-methyl-4-(methoxycarbonyl)-2-aza-1λ⁵-phosphabuta-1,3-diene 

Downstream Products

• 544478-19-5 MRS 1845 
• 50698-12-9 N-methylnitrendipine 
• 131796-81-1 4-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid,ethyl methyl ester 
• 80890-07-9 (+)-Nitrendipine 
• 80873-62-7 (-)-Nitrendipine 
• 89267-41-4 (+/-)-Oxidized Nitrendipine 
• 64603-72-1 SL 5721 
• 74936-72-4 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 64603-74-3 methyl 2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydro-furo<3,4-b>pyridine-3-carboxylate 
• 89288-25-5 ethyl-2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydrofuro<3,4-b>3-pyridinecarboxylate 
• 138135-46-3 (R)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl) ester 5-methyl ester 
• 138135-45-2 (S)-2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl) ester 5-methyl ester 
• 123754-04-1 1,4-dihydro-2,6-bis(1H-imidazol-1-ylmethyl)-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid ethyl methyl diester 

Relevant articles and documents

Facile synthesis of 1,4-dihydropyridine monocarboxylic acids and unsymmetric dicarboxylates via quaternary ammonium salts of 2-aminoethyl 1,4-dihydropyridine-3,5-dicarboxylates

Useful 1,4-dihydropyridine unsymmetric dicarboxylates [nitrendipine (1), nicardipine (2)] and monocarboxylic acid 4 were prepared from unsymmetric 2-aminoethyl methyl 1,4-dihydropyridine-3,5-dicarboxylates 2 and 3 via their corresponding quaternary ammonium salts 5-9.

Preparation method of nitrendipine

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of nitrendipine, which comprises the following steps: adding (E)-2-(3-nitrobenzylidene)-3-oxobutyrate and methyl 3-aminocrotonate into a first solvent, and carrying out a reflux reaction at a first temperature to obtain a first reaction solution; adding acetic anhydride into the first reaction solution at a second temperature to react to obtain a second reaction solution; carrying out a stirring reaction on the second reaction solution at a third temperature, and filtering to obtain a crude product of nitrendipine; and recrystallizing the crude product of nitrendipine to obtain nitrendipine. The invention provides a preparation method of nitrendipine, and aims to effectively controldimethyl ester impurities and diethyl ester impurities, improve the yield and shorten the reaction time so as to improve the productivity.

Preparation method of nitrendipine

The invention belongs to the field of drug synthesis, and particularly relates to a preparation method of nitrendipine. The preparation method is characterized by including following steps: (1), allowing 3-nitrobenzylidene ethyl acetoacetate intermediate and 3-aminomethyl crotonate according to a molar ratio of 1:1-1.1 to react at 70-75 DEG C in advance; (2), adding concentrated hydrochloric acidinto a reaction system of the step (1), and allowing reaction at 70-75 DEG C after adding is completed, wherein adding amount of the concentrated hydrochloric acid is 10-15% of molar weight of the 3-nitrobenzylidene ethyl acetoacetate intermediate; (3), cooling to 15-20 DEG C after reaction in the step (2) is completed, continuing reaction, and performing solid-liquid separation and recrystallization to obtain nitrendipine. Through process control, content of ester exchange impurities can be lowered effectively, and product yield can be increased.