7139-02-8

Basic information

• Product Name: 2,6-Dichloro-4,8-dipiperidinopyrimidino[5,4-d]pyrimidine
• Synonyms: 2,6-Dichloro-4,8-dipiperidinopyrimidino[5,4-d]pyrimidine;2,6-DICHLORO-4,8-DI-1-PIPERIDINYLPYRIMIDO[5,4-D]PYRIMIDINEDIPYRIDAMOLE;Einecs 230-437-4;2,6-Dichloro-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine;PyriMido[5,4-d]pyriMidine,2,6-dichloro-4,8-di-1-piperidinyl-;2,6-dichloro-4,8-dipiperidinyl-pyrimido[5,4-d]pyrimidine
• CAS NO: 7139-02-8
• Molecular Formula: C₁₆H₂₀Cl₂N₆
• Molecular Weight: 367.282
• EINECS: 230-437-4
• Product Categories: Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 7139-02-8.mol
• Article Data: 6

Chemical Properties

• Melting Point: 249-251℃
• Boiling Point: 504.1oC at 760mmHg
• Flash Point: 258.7oC
• Appearance: /
• Density: 1.386 g/cm3
• Vapor Pressure: 2.73E-10mmHg at 25°C
• Refractive Index: 1.643
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 2.00±0.30(Predicted)
• CAS DataBase Reference: 2,6-Dichloro-4,8-dipiperidinopyrimidino[5,4-d]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-Dichloro-4,8-dipiperidinopyrimidino[5,4-d]pyrimidine(7139-02-8)
• EPA Substance Registry System: 2,6-Dichloro-4,8-dipiperidinopyrimidino[5,4-d]pyrimidine(7139-02-8)

Safety Data

• Hazardous Substances Data: 7139-02-8(Hazardous Substances Data)

Usage

Chemical Properties

Beige Solid

Uses

An antitumor nucleoside pyrimido pyrimidine.

InChI:InChI=1/C16H20Cl2N6/c17-15-20-12-11(13(21-15)23-7-3-1-4-8-23)19-16(18)22-14(12)24-9-5-2-6-10-24/h1-10H2

Synthetic route

piperidine (110-89-4) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
With copper(l) iodide; caesium carbonate In nitrobenzene at 180℃; for 16h; Inert atmosphere;	95%
In tetrahydrofuran at 25℃;	93%
Substitution;
In tetrahydrofuran at 0 - 5℃; for 0.333333h;
In tetrachloromethane; acetone at 30℃; for 1h;

C30H34N6O6S2 → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
With thionyl chloride; triethylamine for 0.133333h; Time; Microwave irradiation;	93.5%

1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-(3H,7H)-tetrone → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aq. NaOH / 0.33 h / Heating 1.2: 39 percent / PCl5; POCl3 / 8 h / Heating 2.1: 93 percent / tetrahydrofuran / 25 °C View Scheme

2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine (6713-54-8) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 2 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 View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate; phosphorus trichloride; chlorine / 24 h / 110 °C 2: acetone; tetrachloromethane / 1 h / 30 °C View Scheme

6-Methyluracil (626-48-2) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 6 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 View Scheme
Multi-step reaction with 6 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 View Scheme

orotic acid (65-86-1) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 5 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 View Scheme

5-nitroorotic acid (17687-24-0) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 4 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 View Scheme

5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (7164-43-4) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 View Scheme

orotic acid sodium salt (154-85-8) → 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8)

Conditions	Yield
Multi-step reaction with 5 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 View Scheme

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + (R,S)-2,2-dimethyl-1,3-dioxolane-4-methanol (100-79-8) → 2,6-bis-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine (774539-20-7)

Conditions	Yield
Stage #1: (R,S)-2,2-dimethyl-1,3-dioxolane-4-methanol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	99%

(+/-)-2-methyl-1-butanol (137-32-6) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-bis-(2-methyl-butoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: (+/-)-2-methyl-1-butanol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	98%

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%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + cyclohexylmethyl alcohol (100-49-2) → 2,6-dicyclohexylmethoxy-4,8-dipiperidinopyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: cyclohexylmethyl alcohol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	92%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + 1,2-O-isopropylidene-D-glycerol (14347-78-5) → (S,S)-2,6-bis(2',2'-dimethyl-1',3'-dioxolane-4'-methoxy)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine (774539-21-8)

Conditions	Yield
Stage #1: 1,2-O-isopropylidene-D-glycerol With sodium hydride In tetrahydrofuran at 60℃; for 5h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	92%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + (S)-(+)-(2,2-dimethyl-[1,3]dioxolan-4-yl)methanol (22323-82-6) → (R,R)-2,6-bis(2',2'-dimethyl-1',3'-dioxolane-4'-methoxy)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine (774539-22-9)

Conditions	Yield
Stage #1: (S)-(+)-(2,2-dimethyl-[1,3]dioxolan-4-yl)methanol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	91%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + diethylamine (109-89-7) → N,N,N',N'-tetraethyl-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine-2,6-diamine

Conditions	Yield
In tetrahydrofuran at 200℃; for 96h;	90%

ethanol (64-17-5) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-diethoxy-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: ethanol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	84%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine (93047-01-9)

Conditions	Yield
With potassium hydroxide; hydrogen; palladium on activated charcoal In tetrahydrofuran under 2585.74 Torr; for 48h;	64%

i-Amyl alcohol (123-51-3) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-di-(3'-methylbutoxy)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: i-Amyl alcohol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	63%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + isopropyl alcohol (67-63-0) → 2,6-diisopropoxy-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: isopropyl alcohol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	58%

2,3-dimethoxypropan-1-ol (40453-77-8) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-bis-(2,3-dimethoxy-propoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: 2,3-dimethoxypropan-1-ol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	57%

2-methyl-propan-1-ol (78-83-1) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-diisobutoxy-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: 2-methyl-propan-1-ol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	54%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + trimethyleneglycol (504-63-2) → 3-[6-(3-hydroxy-propoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yloxy]-propan-1-ol

Conditions	Yield
Stage #1: trimethyleneglycol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	51%

methanol (67-56-1) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-dimethoxy-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: methanol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	46%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + ethylene glycol (107-21-1) → 2-[6-(2-hydroxy-ethoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yloxy]-ethanol

Conditions	Yield
Stage #1: ethylene glycol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	45%

propan-1-ol (71-23-8) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 4,8-di-piperidin-1-yl-2,6-dipropoxy-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: propan-1-ol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	42%

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 3-[6-(2,3-dihydroxy-propylamino)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-ylamino]-propane-1,2-diol

Conditions	Yield
at 100 - 150℃;	41%

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + allyl alcohol (107-18-6) → 2,6-bis-allyloxy-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: allyl alcohol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	40%

2-methoxy-ethanol (109-86-4) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-bis-(2-methoxy-ethoxy)-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: 2-methoxy-ethanol With sodium hydride In tetrahydrofuran at 60℃; for 0.0833333h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	34%

1-methoxy-2-propanol (107-98-2) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,6-di-(1'-methyl-2'-methoxy)ethoxy-4,8-dipiperidinopyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: 1-methoxy-2-propanol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;	22%

(2-hydroxyethyl)(methyl)amine (109-83-1) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → 2,2'-[N,N'-dimethyl-N,N'-(4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine-2,6-diyl)-diamino]-bis-ethanol (13144-60-0)

Conditions	Yield
Substitution;

n-Dodecylamine (124-22-1) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → (6-chloro-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yl)-dodecyl-amine

Conditions	Yield
Substitution;

n-Octylamine (111-86-4) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → (6-chloro-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yl)-octyl-amine

Conditions	Yield
Substitution;

hexan-1-amine (111-26-2) + 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) → (6-chloro-4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidin-2-yl)-hexyl-amine

Conditions	Yield
Substitution;

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + ethanolamine (141-43-5) → 2,2'-(4,8-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine-2,6-diyldiamino)-bis-ethanol (57370-13-5)

Conditions	Yield
Substitution;
In dimethyl sulfoxide at 150℃; for 6h;	162 mg

2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine (7139-02-8) + (S)-2-O-(4'-methoxybenzyl)propan-1,2-diol (122151-36-4) → (S,S)-2,6-di-[2'-O-(4'-methoxybenzyl)propoxy]-4,8-dipiperidinopyrimido[5,4-d]pyrimidine (774539-31-0)

Conditions	Yield
Stage #1: (S)-2-O-(4'-methoxybenzyl)propan-1,2-diol With sodium In tetrahydrofuran for 2h; Stage #2: 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine In tetrahydrofuran Heating;

Upstream product

• 154-85-8 orotic acid sodium salt 
• 7164-43-4 5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid 
• 17687-24-0 5-nitroorotic acid 
• 65-86-1 orotic acid 
• 626-48-2 6-Methyluracil 
• 6713-54-8 2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine 
• 110-89-4 piperidine 
• 32980-71-5 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine 

Downstream Products

• 774539-31-0 (S,S)-2,6-di-[2'-O-(4'-methoxybenzyl)propoxy]-4,8-dipiperidinopyrimido[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 
• 58-32-2 dipyridamole 
• 57370-13-5 2,6-Bis(diethanolamino)-4,8-dipiperidino-pyrimidino<5,4-d>pyrimidin 

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The invention provides a production method of a bulk drug of dipyridamole, which relates to the field of the synthesis of chemical bulk drugs. The production method comprises the following steps: protecting carbonyl of urea, performing condensation reaction with 2,3-diaminosuccinic acid, performing chlorination for hydroxyl of a condensation reactant, replacing chlorine with piperidine, hydrolyzing an obtained product, obtaining a compound containing two carbonyls, separating the product, enabling the separated product to have condensation reaction with diethanol amine, obtaining dipyridamole,and refining to obtain a finished product. By adopting the production method, the synthetic procedure of the dipyridamole is simplified, the conversion rate of raw materials can be greatly increased,and the production cost is decreased.

Novel technology with introduced catalyst to optimize synthesis of dipyridamole

The invention discloses a novel technology with an introduced catalyst to optimize the synthesis of dipyridamole, and belongs to the technical field of medical intermediates. According to the technology, in the step of oxidizing a methyl group of 6-methyl uracil into formic acid, a Co(OAc)2/HOAc/AIBN/O2 catalytic system is introduced, and the reaction yield is increased to 90 to 95%. In the step of reducing a nitro group of nitro-orotic acid into an amino group, activated copper powder is taken as the catalyst, the yield is more than 85%; and moreover, the environmental pollution and danger caused by sodium hydrosulfite are avoided. In the step of converting substituted hydroxyl group into substituted chlorine, SOCl12 and N,N-dimethyl formamide are introduced into the reaction system so as to reduce the environment pollution and the difficulty of post treatment. In the reactions of preparing 2,6-dichloro-4,8-bis(piperidine-1-yl)pyrimido[5,4-d]pyrimidine from perchloro pyrimido[5,4-d]pyrimidine, a CuI/PhNO2 catalytic system is introduced into the reaction system, the reaction yield reaches 95%, moreover, the operation is easy, and the treatment is simple. The provided technology increases the yield, reduces the cost, guarantees the safety, saves the energy, and meets the requirements of green reactions and modern chemical production.

Resistance-modifying agents. 11. Pyrimido[5,4-d]pyrimidine modulators of antitumor drug activity. Synthesis and structure-activity relationships for nucleoside transport inhibition and binding to α1-acid glycoprotein

The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, α1-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of 3H-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4?-methoxybenzylamino, 3?,4?-dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.