58-32-2

Basic information

• Product Name: Dipyridamole
• Synonyms: Dipyridamole (200 mg);2,2',2'',2'''-((4,8-Di(piperidin-1-yl)pyriMido[5,4-d]pyriMidine-2,6-diyl)bis(azanetriyl))tetraethanol;DypyridaMole API;2,6-Bis(diethanolamine)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine 2,2',2'',2'''-[(4,8-Dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetrakisethanol;2,2',2'',2'''-((4,8-Di(piperidin-1-yl)pyrimido[5,4-d]-pyrimidine-2,6-diyl)bis(azanetriyl))tetraet;C24H4ON804;2,2',2'',2'''-((4,8-Di(piperidin-1-yl)pyrimido[5,4-d]-pyrimidine-2,6-diyl)bis(azanetriyl))tetr;2,2',2'',2'''-[(4,8-Dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
• CAS NO: 58-32-2
• Molecular Formula: C₂₄H₄₀N₈O₄
• Molecular Weight: 504.63
• EINECS: 200-374-7
• Product Categories: Pharmaceutical intermediate;Heterocycle-Pyrimidine series;PERSANTINE;Cardiovascular APIs;Pyridines;Organics;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Phosphodiesterase Inhibitors;Cyclic Nucleotide Metabolism;G Proteins and Cyclic Nucleotides;Cyclic Nucleotide related
• Mol File: 58-32-2.mol
• Article Data: 10

Chemical Properties

• Melting Point: 165-166 °C(lit.)
• Boiling Point: 593.96°C (rough estimate)
• Flash Point: 441.5 °C
• Appearance: yellow/powder
• Density: 1.2046 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6910 (estimate)
• Storage Temp.: −20°C
• Solubility: DMSO: soluble
• PKA: pKa 6.4 (Uncertain)
• Water Solubility: Soluble in chloroform, methanol, dilute acids, ethanol. Slightly soluble in water.
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• Merck: 14,3346
• CAS DataBase Reference: Dipyridamole(CAS DataBase Reference)
• NIST Chemistry Reference: Dipyridamole(58-32-2)
• EPA Substance Registry System: Dipyridamole(58-32-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• RTECS: KK7450000
• Hazardous Substances Data: 58-32-2(Hazardous Substances Data)

Usage

Description

Dipyridamole (58-32-2) is a phosphodiesterase inhibitor (IC50=0.37, 0.38, 0.45, 0.9 and 4.5 μM for PDE11, 6, 10, 5 and 8 respectively.1,2 Potent equilibrative nucleoside transporter 1 (ENT1) inhibitor Ki=8.2 nM vs. 144.8 nM for ENT1 and ENT2 respectively.3 Antiplatelet activity.4

Chemical Properties

Yellow Powder

Originator

Persantine,Boehringer Ingelheim,US,1961

Uses

Different sources of media describe the Uses of 58-32-2 differently. You can refer to the following data:
1. Dipiridamol is known as a coronary vasodilating agent, although it also possesses specific antiaggregant activity. It is used for preventing thrombo-formation after cardiac valve replacement in combination with warfarin.
2. Dipyridamole prevents platelets sticking to the replacement heart valve and causing a blood clot on the valve. It is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease. This compound has been shown to suppress high glucose-induced osteopontin mRNA expression and protein secretion, as well as inhibit cAMP and cGMP hydrolysis. Research indicates that Dipyridamole is a non-specific nucleoside transport inhibitor with the ability to increase the effects of adenosine in sinoatrial and atrioventricular nodes. Dipyridamole is an inhibitor of ENT1 and ENT2.
3. Selective inhibitor of phosphodiesterase V (PDE 5); potent coronary vasodilator drug; adenosine transport inhibitor; inhibitor of platelet aggregation
4. A phosphodiester, cGMP, and non-specific nucleoside transport inhibitor

Definition

ChEBI: A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots.

Manufacturing Process

Urea may be reacted with acetoacetic ester and that product nitrated to give 5-nitro-orotec acid. That is hydrogenated, then reacted with urea and potassium cyanate to give tetrahydroxypyrimidopyrimidine. The tetrahydroxy compound is converted to the tetrachloro compound POCl3. Reaction with diethanolamine and then with piperidine gives dipyridamole.

Brand name

Persantine (Boehringer Ingelheim).

Therapeutic Function

Coronary vasodilator

General Description

Dipyridamole, 2,2',2',2'''-[(4,8-di-1piperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]-tetrakisethanol (Persantine), may be used for coronary andmyocardial insufficiency. Its biggest use today, however, isas an antithrombotic in patients with prosthetic heart valves.It is a bitter, yellow, crystalline powder, soluble in diluteacids, methanol, or chloroform. A formulation containingdipyridamole and aspirin (Aggrenox) is currently beingmarketed as an antithromobotic.Dipyridamole is a long-acting vasodilator. Its vasodilatingaction is selective for the coronary system; it is indicatedfor long-term therapy of chronic angina pectoris. Thedrug also inhibits adenosine deaminase in erythrocytesand interferes with the uptake of the vasodilator adenosineby erythrocytes. These actions potentiate the effect ofprostacyclin (PGI2), which acts as an inhibitor to plateletaggregation.

Biological Activity

Coronary vasodilator; adenosine transport inhibitor. Phosphodiesterase inhibitor (IC 50 values are 0.37, 0.38, 0.45, 0.9 and 4.5 μ M? for PDE11, 6, 10, 5 and 8 respectively).

Biochem/physiol Actions

Selective inhibitor of phosphodiesterase V (PDE 5); potent coronary vasodilator drug; adenosine transport inhibitor; inhibitor of platelet aggregation.

Mechanism of action

Dipyridamole exerts its antiplatelet function by increasing cellular concentrations of cAMP via its inhibition of the degradating enzyme, cyclic nucleotide PDE3. It also blocks adenosine uptake, which acts at A2 adenosine receptors to stimulate platelet adenyl cyclase. Less common uses for this drug include inhibition of embolization from prosthetic heart valves when used in combination with warfarin (the only currently recommended use) and reduction of thrombosis in patients with thrombotic disease when used in combination with aspirin. Alone, dipyridamole has little, if any, benefit in the treatment of thrombotic conditions.

Clinical Use

Dipyridamole is a pyrimidopyrimidine derivative with vasodilatory and antiplatelet properties.

Safety Profile

Poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion and subcutaneous routes. Human systemic effects cardiomyopathy including infarction. Mutation data reported. Used as a coronary vasodilator. When heated to decomposition it e

Synthesis

Dipyridamole, 2,2',2'',2'''-[(4,8-dipiperidinopirimido[5,4-d]pirimidin-2,6- diyl)-diimino]-tetraethanol (19.4.13), is easily synthesized from 5-nitroorotic acid (19.4.8), easily obtained, in turn, by nitrating of 2,4-dihydroxy-6-methylpyrimidine, which is usually synthesized by the condensation of urea with acetoacetic ether. Reduction of the nitro group in 5-nitroorotic acid by various reducing agents gives 5-aminoorotic acid (19.4.9), which is reacted with urea or with potassium cyanide to give 2,4,6,8- tetrahydroxypyrimido[5,4-d]pyrimidine (19.4.10). This undergoes a reaction with a mixture of phosphorous oxychloride and phosphorous pentachloride, which forms 2,4,6,8- tetrachloropyrimido[ 5,4-d]pyrimidine (19.4.11). Reacting the resulting tetrachloride with piperidine replaces the chlorine atoms at C4 and C8 of the heterocyclic system with piperidine, giving 2,6-dichloropyrimido-4,8-dipiperidino[5,4-d]pyrimidine (19.4.12). Reacting the resulting product with diethanolamine gives dipyridamole (19.4.13).

Drug interactions

Potentially hazardous interactions with other drugsAnti-arrhythmics: effects of adenosine enhanced and extended.Anticoagulants: anticoagulant effect of coumarins, phenindione and heparin enhanced.

Metabolism

Dipyridamole is metabolised in the liver. Renal excretion of the parent compound is negligible (< 0.5%). Urinary excretion of the glucuronide metabolite is low (5%), the metabolites are mostly (about 95%) excreted via the bile into the faeces, with some evidence of entero-hepatic recirculation.

References

1) Fujishige et al. (1999), Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A); J. Biol. Chem., 274 18438 2) Soderling et al. (1998), Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase; Proc. Natl. Acad. Sci. USA, 95 8991 3) Lin and Buolamwini (2007), Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.; J. Med. Chem., 50 3906 4) Coccheri (2010), Antiplatelet drugs – do we need new options? With a reappraisal of direct thromboxane inhibitors; Drugs, 70 887

InChI:InChI=1/C24H40N8O4/c1-15(33)31(16(2)34)23-25-19-20(21(27-23)29-11-7-5-8-12-29)26-24(32(17(3)35)18(4)36)28-22(19)30-13-9-6-10-14-30/h15-18,33-36H,5-14H2,1-4H3

Synthetic route

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + 2,2'-iminobis[ethanol] (111-42-2) → dipyridamole (58-32-2)

Conditions	Yield
Stage #1: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine; 2,2'-iminobis[ethanol] In toluene at 0 - 155℃; for 9.5h; Stage #2: With benzenesulfonic acid In water; toluene at 0 - 95℃; for 2h; Stage #3: With ammonia; pyrographite In ethanol for 0.333333h; pH=8; Temperature;	95%
With 001x7 strong acid cation exchange resin In 1,3-dioxane at 78℃; for 4.5h; Temperature;	75%
Stage #1: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine; 2,2'-iminobis[ethanol] at 180℃; for 3h; Stage #2: With sodium hydroxide In water; acetone at 25℃; for 4h;	70%

C16H24N6O2 + 2,2'-iminobis[ethanol] (111-42-2) → dipyridamole (58-32-2)

Conditions	Yield
With hydrogen at 240℃; under 11251.1 Torr; for 3h;	50.31%

piperidine (110-89-4) + 2-<2,6-dihydroxy-3,5-dimethyl-phenoxy>-3,5-dinitro-benzophenone → dipyridamole (58-32-2)

Conditions	Yield
1: Substitution / 2: Substitution;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → dipyridamole (58-32-2)

Conditions	Yield
1: Substitution / 2: Substitution;
Multi-step reaction with 2 steps 1: acetone; tetrachloromethane / 1 h / 30 °C 2: 0.25 h / 200 °C View Scheme

2,2'-(6-chloro-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-ylazanediyl)-bis-ethanol (54093-92-4) + 2,2'-iminobis[ethanol] (111-42-2) → dipyridamole (58-32-2)

Conditions	Yield
at 25 - 115℃;

2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine (6713-54-8) → dipyridamole (58-32-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 1,4-dioxane / 1 h 1.2: 1.5 h / Darkness 2.1: caesium carbonate; copper(l) iodide / nitrobenzene / 16 h / 180 °C / Inert atmosphere 3.1: 3 h / 180 °C 3.2: 4 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 2: acetone; tetrachloromethane / 1 h / 30 °C 3: 0.25 h / 200 °C View Scheme

6-Methyluracil (626-48-2) → dipyridamole (58-32-2)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 2,2'-azobis(isobutyronitrile); cobalt(II) acetate; acetic acid; oxygen / 15 h / 80 °C 2.1: sodium hydroxide / water / 3 h 2.2: 25 - 45 °C / Inert atmosphere 3.1: copper; hydrogenchloride / water / 13 h / 40 °C / Inert atmosphere 4.1: sodium hydroxide / water / 4 h / 100 °C 5.1: thionyl chloride / 1,4-dioxane / 1 h 5.2: 1.5 h / Darkness 6.1: caesium carbonate; copper(l) iodide / nitrobenzene / 16 h / 180 °C / Inert atmosphere 7.1: 3 h / 180 °C 7.2: 4 h / 25 °C View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydroxide; water; oxygen / 95 °C 2.1: nitric acid; sulfuric acid / 1 h / 10 - 30 °C 3.1: sodium dithionite / water / 0.5 h / 35 °C 4.1: 0.33 h / 100 °C 4.2: 1 h / 90 - 100 °C 4.3: 0.5 h / 60 °C / pH 4 5.1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 6.1: acetone; tetrachloromethane / 1 h / 30 °C 7.1: 0.25 h / 200 °C View Scheme

orotic acid (65-86-1) → dipyridamole (58-32-2)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: sodium hydroxide / water / 3 h 1.2: 25 - 45 °C / Inert atmosphere 2.1: copper; hydrogenchloride / water / 13 h / 40 °C / Inert atmosphere 3.1: sodium hydroxide / water / 4 h / 100 °C 4.1: thionyl chloride / 1,4-dioxane / 1 h 4.2: 1.5 h / Darkness 5.1: caesium carbonate; copper(l) iodide / nitrobenzene / 16 h / 180 °C / Inert atmosphere 6.1: 3 h / 180 °C 6.2: 4 h / 25 °C View Scheme

5-nitroorotic acid (17687-24-0) → dipyridamole (58-32-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: copper; hydrogenchloride / water / 13 h / 40 °C / Inert atmosphere 2.1: sodium hydroxide / water / 4 h / 100 °C 3.1: thionyl chloride / 1,4-dioxane / 1 h 3.2: 1.5 h / Darkness 4.1: caesium carbonate; copper(l) iodide / nitrobenzene / 16 h / 180 °C / Inert atmosphere 5.1: 3 h / 180 °C 5.2: 4 h / 25 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium dithionite / water / 0.5 h / 35 °C 2.1: 0.33 h / 100 °C 2.2: 1 h / 90 - 100 °C 2.3: 0.5 h / 60 °C / pH 4 3.1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 4.1: acetone; tetrachloromethane / 1 h / 30 °C 5.1: 0.25 h / 200 °C View Scheme

5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (7164-43-4) → dipyridamole (58-32-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water / 4 h / 100 °C 2.1: thionyl chloride / 1,4-dioxane / 1 h 2.2: 1.5 h / Darkness 3.1: caesium carbonate; copper(l) iodide / nitrobenzene / 16 h / 180 °C / Inert atmosphere 4.1: 3 h / 180 °C 4.2: 4 h / 25 °C View Scheme
Multi-step reaction with 4 steps 1.1: 0.33 h / 100 °C 1.2: 1 h / 90 - 100 °C 1.3: 0.5 h / 60 °C / pH 4 2.1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 3.1: acetone; tetrachloromethane / 1 h / 30 °C 4.1: 0.25 h / 200 °C View Scheme

orotic acid sodium salt (154-85-8) → dipyridamole (58-32-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: nitric acid; sulfuric acid / 1 h / 10 - 30 °C 2.1: sodium dithionite / water / 0.5 h / 35 °C 3.1: 0.33 h / 100 °C 3.2: 1 h / 90 - 100 °C 3.3: 0.5 h / 60 °C / pH 4 4.1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 5.1: acetone; tetrachloromethane / 1 h / 30 °C 6.1: 0.25 h / 200 °C View Scheme

acetyl chloride (75-36-5) + dipyridamole (58-32-2) → 2,2',2'',2'''-tetrakis-acetoxy-1,1',1'',1'''-(4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2,6-diylbisazanediyl)-tetrakis-ethane (63023-20-1)

Conditions	Yield
dmap In tetrahydrofuran at 0 - 5℃; for 3h;	95%

toluene-4-sulfonic acid (104-15-4) + dipyridamole (58-32-2) → dipyridamole di-p-toluenesulfonate

Conditions	Yield
In tetrahydrofuran	93.7%

formic acid (64-18-6) + dipyridamole (58-32-2) → 2,2',2'',2'''-tetrakis-formyloxy-1,1',1'',1'''-(4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine-2,6-diylbisazanediyl)-tetrakis-ethane (107628-98-8)

Conditions	Yield
for 6h; Heating;	92%

maleic acid (110-16-7) + dipyridamole (58-32-2) → C24H40N8O4*C4H4O4

Conditions	Yield
In isopropyl alcohol	91.3%

propyl bromide (106-94-5) + dipyridamole (58-32-2) → C36H64N8O4

Conditions	Yield
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: propyl bromide In N,N-dimethyl-formamide Further stages.;	85%

dipyridamole (58-32-2) + methyl iodide (74-88-4) → N2,N2,N6,N6-tetrakis(2-methoxyethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine

Conditions	Yield
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide for 1h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	84%
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 25℃; for 4h;	69%
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: methyl iodide In N,N-dimethyl-formamide Further stages.;	64%

ethyl bromide (74-96-4) + dipyridamole (58-32-2) → C32H56N8O4

Conditions	Yield
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: ethyl bromide In N,N-dimethyl-formamide Further stages.;	84%

dipyridamole (58-32-2) → 2-[{6-[Bis-(2-hydroxy-ethyl)-amino]-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yl}-(2-hydroxy-ethyl)-amino]-ethanol; hydrochloride (59681-39-9)

Conditions	Yield
With hydrogenchloride In isopropyl alcohol	62.7%

dipyridamole (58-32-2) → C24H40N8O4*2H2O4S

Conditions	Yield
With sulfuric acid In isopropyl alcohol	58.6%

dipyridamole (58-32-2) + isopropyl bromide (75-26-3) → C30H52N8O4

Conditions	Yield
Stage #1: dipyridamole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide Further stages.;	55%

dipyridamole (58-32-2) + benzenesulfonic acid (98-11-3) → C24H40N8O4*2C6H6O3S

Conditions	Yield
In isopropyl alcohol	48.6%

dipyridamole (58-32-2) → C24H40N8O4*2H3O4P

Conditions	Yield
With phosphoric acid In isopropyl alcohol	47%

dipyridamole (58-32-2) + 3-Methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid (194596-99-1) → 2,6-bis(diethyl-3-methyl-3(2,4,6-trimethoxyphenylmethylthio)butyric acid ester amino)-4,8-dipiperidinopyrimido-[5,4-d]-pyrimidine

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 50℃; for 44h;	23%

acetic anhydride (108-24-7) + dipyridamole (58-32-2) → 2,2',2'',2'''-tetrakis-acetoxy-1,1',1'',1'''-(4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2,6-diylbisazanediyl)-tetrakis-ethane (63023-20-1)

Conditions	Yield
With pyridine Ambient temperature;	0.067 g

dipyridamole (58-32-2) → 1-{2,6-bis-[bis-(2-hydroxy-ethyl)-amino]-8-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-4-yl}-piperidin-2-one

Conditions	Yield
With dihydrogen peroxide; 5-amino-2,3-dihydrophthalazine-1,4-dione; sodium chloride In phosphate buffer at 37℃; pH=7.4; Product distribution; Kinetics; Further Variations:; Reagents;

tartaric acid (87-69-4) + dipyridamole (58-32-2) → dipyridamole tartaric acid monoester + C32H48N8O14

Conditions	Yield
With water In neat (no solvent, solid phase) at 40℃; for 240h;

Upstream product

• 7139-02-8 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine 
• 111-42-2 2,2'-iminobis[ethanol] 
• 110-89-4 piperidine 
• 32980-71-5 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine 
• 54093-92-4 2,2'-(6-chloro-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-ylazanediyl)-bis-ethanol 
• 6713-54-8 2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine 
• 626-48-2 6-Methyluracil 
• 65-86-1 orotic acid 
• 17687-24-0 5-nitroorotic acid 
• 7164-43-4 5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid 
• 154-85-8 orotic acid sodium salt 

Downstream Products

• 49845-74-1 dipyridamole di-p-toluenesulfonate 

Relevant articles and documents

Efficient synthesis method of dipyridamole

The invention discloses an efficient synthesis method of dipyridamole. The method comprises the following steps: dissolving a dichloro compound and diethanol amine into a solvent 1,3-dioxane to form ahomogeneous reactant; adding a catalyst, namely 001*7 strongly acidic cation exchange resin in the process of a reaction, wherein a reaction temperature is 75-80 DEG C, reaction time is 4-5 hours, and the content of a crude product reaches 95%; carrying out filtering to directly remove diethanol amine hydrochloride; filtering out the cation exchange resin by using a small bag filter, and washingand drying the cation exchange resin so as to recycling the cation exchange resin; drying a filtered crude product in a tray oven at 70-80 DEG C, recycling the solvent for indiscriminate usage, and adding ethanol accounting for 1.5 times of the weight of the dried crude product; carrying out heating to 78-80 DEG C, performing refluxing and dissolving, then conducting cooling to 15-20 DEG C, and performing crystallizing to obtain a finished product. The method is simple in process, beneficial for reducing energy consumption, safe and environment-friendly to operate, low in by-product amount, high in yield and convenient for industrial production.

Preparation method for dipyridamole

The invention belongs to the chemical field, and particularly relates to a preparation method for dipyridamole; diethanol amine and 2,6-dichloro-4,8-dipiperidinopyrimidino[5,4-D]pyrimidine are subjected to a reaction at relatively low temperature to generate dipyridamole, the dipyridamole crude product is subjected to secondary refining, and the yield and the chemical purity of the finally obtained dipyridamole are respectively increased to 94% or more and 98% or more; and the preparation method has the advantages of mild reaction, high reaction efficiency, low cost and the like, and is suitable for wide promotion and application.

PROCESSES FOR THE PREPARATION OF DIPYRIDAMOLE

The present invention relates to the active pharmaceutical ingredient dipyridamole. In particular, it relates to efficient processes for the preparation of dipyridamole which are amenable to large scale commercial production and provide the required product with improved yield and purity. The present invention also relates to a novel crystallization method for the purification of dipyridamole.