32980-71-5

Basic information

• Product Name: 2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE
• Synonyms: 2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE;tetrachloropyrimidopyrimidine;tetrachloropyrimido[5,4-d]pyrimidine;2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE 97+%;2,4,6,8-Tetrachloro-1,3,5,7-tetraazanaphthalene;Nsc96654;Pyrimido[5,4-D]pyrimidine, 2,4,6,8-tetrachloro-;Pyrimido[5,4-D]pyrimidine, tetrachloro-
• CAS NO: 32980-71-5
• Molecular Formula: C₆Cl₄N₄
• Molecular Weight: 269.9
• EINECS: 251-318-3
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 32980-71-5.mol
• Article Data: 7

Chemical Properties

• Melting Point: 254-258 °C
• Boiling Point: 335.1 °C at 760 mmHg
• Flash Point: 186.8 °C
• Appearance: /
• Density: 1.871g/cm³
• Vapor Pressure: 0.000237mmHg at 25°C
• Refractive Index: 1.704
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly)
• PKA: -3.88±0.30(Predicted)
• Stability: Moisture Sensitive
• CAS DataBase Reference: 2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE(32980-71-5)
• EPA Substance Registry System: 2,4,6,8-TETRACHLOROPYRIMIDO[5,4-D]PYRIMIDINE(32980-71-5)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 32980-71-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 32980-71-5 differently. You can refer to the following data:
1. Potential tyrosine kinase signal transduction inhibitor. A pyrimido[5,4-d]pyrimidine derivative used as an intermediate in the preparation of nucleoside transporter 1 inhibitors and potential modulators of the activity of antimetabolite antitumor agents.
2. Potential tyrosine kinase signal transduction inhibitor.A pyrimido[5,4-d]pyrimidine derivative used as an intermediate in the preparation of nucleoside transporter 1 inhibitors and potential modulators of the activity of antimetabolite antitumor agents.

InChI:InChI=1/C6Cl4N4/c7-3-1-2(12-6(10)13-3)4(8)14-5(9)11-1

Synthetic route

2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine (6713-54-8) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Stage #1: 2,4,6,8-tetrahydroxypyrimidine-[5,4-d]pyrimidine With thionyl chloride In 1,4-dioxane for 1h; Stage #2: With N,N-dimethyl-formamide In 1,4-dioxane for 1.5h; Darkness;	88.59%
With phosphorus pentachloride; trichlorophosphate at 145℃; for 25.5h;	37%
With chlorine; trichlorophosphate; phosphorus trichloride at 110℃; for 24h;

3,7-disodio-1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-(3H,7H)-tetralone → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate for 15h; Heating;	51%

1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-(3H,7H)-tetrone → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Stage #1: 1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-(3H,7H)-tetrone With sodium hydroxide for 0.333333h; Heating; Stage #2: With phosphorus pentachloride; trichlorophosphate for 8h; Heating;	39%

sodium-salt of 1,5-dihydro-pyrimido<5,4-d>pyrimidine-2,4,6,8-tetraone → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate
With phosphorus pentachloride; trichlorophosphate

5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (7164-43-4) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aq. ammonium chloride / 1 h / 140 - 210 °C 1.2: 73 percent / aq. NaOH / Heating 2.1: 51 percent / POCl3; PCl5 / 15 h / Heating View Scheme
Multi-step reaction with 2 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 View Scheme

5-aminoorotic acid (7164-43-4) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-benzyl-N,N,N-triethylammonium chloride; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol / 9 h / 150 - 160 °C 2: phosphorus pentachloride; trichlorophosphate / 25.5 h / 145 °C View Scheme

6-Methyluracil (626-48-2) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Multi-step reaction with 5 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 View Scheme
Multi-step reaction with 5 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 View Scheme

orotic acid (65-86-1) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme

5-nitroorotic acid (17687-24-0) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

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

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

Conditions	Yield
With hydrogenchloride In water for 24h; Reflux;	105 g

orotic acid sodium salt (154-85-8) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme

C6N4O4(4-)*2Na(1+)*2H(1+) → 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5)

Conditions	Yield
With phosphorus derivatives In N,N-dimethyl-formamide at 106 - 150℃; for 6h;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 4-methoxy-benzylamine (2393-23-9) → 4,8-bis(benzylamino)-2,6-dichloropyrimido[5,4-d]pyrimidine (94542-24-2)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 1h;	98%

propylamine (107-10-8) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-N4,N8-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 1h;	97%
In tetrahydrofuran at 0 - 5℃; for 0.333333h;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + propan-1-ol-3-amine (156-87-6) → 3-(2,6,8-trichloropyrimido[5,4-d]pyrimidin-4-ylamino)propan-1-ol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78 - 20℃; for 0.5h;	97%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + methylamine (74-89-5) → 2,6-dichloro-N4,N8-dimethyl-pyrimido[5,4-d]pyrimidine-4,8-diamine (500860-54-8)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 2h;	96%
In tetrahydrofuran at 0 - 5℃; for 0.333333h;
In tetrahydrofuran at 0 - 20℃; for 1h; Concentration; Temperature;

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;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + benzylamine (100-46-9) → 4,8-bis(benzylamino)-2,6-dichloropyrimido[5,4-d]pyrimidine (94542-24-2)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	93%
With potassium carbonate In tetrahydrofuran at 25℃; for 0.333333h;	69%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 4-methoxy-benzylamine (2393-23-9) → 2,6-dichloro-4,8-di-(4'-methoxybenzylamino)pyrimido[5,4-d]pyrimidine (213840-32-5)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	93%

propylamine (107-10-8) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → propyl (2,6,8-trichloropyrimido[5,4-d]pyrimidin-4-yl)amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.833333h;	93%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + ethylamine (75-04-7) → 2,6-dichloro-N4,N8-diethyl-pyrimido[5,4-d]pyrimidine-4,8-diamine

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 2h;	92%
In tetrahydrofuran at 0 - 20℃; for 1h;	88%
In tetrahydrofuran at 0 - 5℃; for 0.333333h;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 1-Amino-2-methyl-propan-2-ol (2854-16-2) → 2-methyl-1-(2,6,8-trichloropyrimido[5,4-d]pyrimidin-4-ylamino)propan-2-ol

Conditions	Yield
Stage #1: 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine; 1-Amino-2-methyl-propan-2-ol In tetrahydrofuran at -78℃; for 0.5h; Stage #2: With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 0.5h;	92%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 1-amino-2-propene (107-11-9) → N4,N8-diallyl-2,6-dichloro-pyrimido[5,4-d]pyrimidine-4,8-diamine

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 2h;	91%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6,8-Trichloropyrimido[5,4-d]pyrimidin-4-ol

Conditions	Yield
With water In tetrahydrofuran at 20℃; for 24h;	91%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + ethanolamine (141-43-5) → 2-(2,6,8-trichloropyrimido[5 ,4-d]pyrimidin-4-ylamino)ethanol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 2h;	88%

n-Octylamine (111-86-4) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-4,8-bis(N-octylamino)pyrimido[5,4-d]pyrimidine (218305-19-2)

Conditions	Yield
In chloroform for 0.5h; cooling;	87%
In chloroform at 10℃; for 0.833333h;	86%

4-methoxy-N-methylbenzylamine (702-24-9) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-4,8-di-(N-4'-methoxybenzyl-N-methylamino)pyrimido[5,4-d]pyrimidine (213840-39-2)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	87%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + dibenzylamine (103-49-1) → 2,6-dichloro-4,8-bis-(dibenzylamino)pyrimido[5,4-d]pyrimidine (774539-00-3)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	87%
In tetrahydrofuran at 0 - 5℃; for 0.333333h;

n-Dodecylamine (124-22-1) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-4,8-bis(N-dodecylamino)pyrimido[5,4-d]pyrimidine

Conditions	Yield
In chloroform at 10℃;	86%
In chloroform cooling;	86%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 3,4-dimethoxybenzylamine (5763-61-1) → 2,6-dichloro-N4,N8-bis(3,4-dimethoxybenzyl)pyrimido[5,4-d]pyrimidine-4,8-diamine (213840-35-8)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	83%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + p-Trifluoromethylbenzylamine (3300-51-4) → 2,6-dichloro-4,8-di-(4'-trifluoromethylbenzylamino)pyrimido[5,4-d]pyrimidine (213840-34-7)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	81%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + phenylboronic acid (98-80-6) → C18H10Cl2N4

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene at 120℃; for 3h;	77%

[2-fluoro-4-(methylthio)phenyl]amine (76180-33-1) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6,8-trichloro-N-(2-fluoro-4-(methylsulfonyl)phenyl)pyrimido[5,4-d]pyrimidin-4-amine

Conditions	Yield
Stage #1: [2-fluoro-4-(methylthio)phenyl]amine; 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine In tetrahydrofuran; water at 0 - 20℃; for 1h; Stage #2: With 3-chloro-benzenecarboperoxoic acid In tetrahydrofuran; dichloromethane; water at 0 - 20℃;	77%

N-methylhexanamine (35161-70-7) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 2,6-dichloro-4,8-bis(N-methylhexylamino)pyrimido[5,4-d]pyrimidine

Conditions	Yield
In chloroform cooling;	76%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + cyclopropanemethylamine (2516-47-4) → 2,6-dichloro-N4,N8-bis-cyclopropylmethyl-pyrimido[5,4-d]pyrimidine-4,8-diamine

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 3h;	76%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + N-benzyl-N-(3,4-dimethoxybenzyl)amine (13174-24-8) → 2,6-dichloro-4,8-di-(N-benzyl-N-3',4'-dimethoxybenzylamino)pyrimido[5,4-d]pyrimidine (774539-01-4)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	74%
With potassium carbonate In tetrahydrofuran at 25℃; for 1h; Substitution;

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + 2,2'-iminobis[ethanol] (111-42-2) → 2,6-dichloro-4,8-bis-(diethanoloamino)pyrimido[5,4-d]pyrimidine (68030-10-4)

Conditions	Yield
In tetrahydrofuran at 25℃;	74%

4-cyano-2-fluoroaniline (63069-50-1) + 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) → 3-fluoro-4-((2,6,8-trichloropyrimido[5,4-d]pyrimidin-4-yl)amino)benzonitrile

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 1h;	74%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + benzylamine (100-46-9) → 4-benzylamino-2,6,8-trichloropyrimido[5,4-d]pyrimidine (419574-99-5)

Conditions	Yield
With potassium carbonate In tetrahydrofuran for 0.166667h;	72%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + benzyl-methyl-amine (103-67-3) → 2,6-dichloro-4,8-di-(N-benzyl-N-methylamino)pyrimido[5,4-d]pyrimidine (213840-37-0)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 25℃;	72%

2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine (32980-71-5) + (R,S)-2,2-dimethyl-1,3-dioxolane-4-methanol (100-79-8) → 2,6-dichloro-4,8-bis([R,S]2,2'-dimethyl-1',3'-dioxolane-4'-methoxy)pyrimido[5,4-d]pyrimidine

Conditions	Yield
Stage #1: (R,S)-2,2-dimethyl-1,3-dioxolane-4-methanol With sodium hydride In tetrahydrofuran at 50 - 60℃; for 0.166667h; Stage #2: 2,4,6,8-Tetrachloro-pyrimido[5,4-d]pyrimidine In tetrahydrofuran for 0.5h;	72%

Upstream product

• 7164-43-4 5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid 
• 7164-43-4 5-aminoorotic acid 
• 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 
• 154-85-8 orotic acid sodium salt 

Downstream Products

• 7139-02-8 2,6-dichloro-4,8-bis(piperidin-1-yl)pyrimido[5,4-d]pyrimidine 
• 93819-72-8 2,6-dichloro-N,N'-diphenyl-pyrimido[5,4-d]pyrimidine-4,8-diamine 
• 54093-81-1 2,6-dichloro-4,8-di-morpholin-4-yl-pyrimido[5,4-d]pyrimidine 
• 28753-34-6 2,4,6,8-tetra-piperidin-1-yl-pyrimido[5,4-d]pyrimidine 
• 36926-31-5 4,8-dichloro-2,6-di-piperidin-1-yl-pyrimido[5,4-d]pyrimidine 

Relevant articles and documents

2,6-bis(diethanolamine)-4,8-dipiperidine-pyrimidine-[5,4-d]pyrimidine synthetic method

The invention discloses a 2,6-bis(diethanolamine)-4,8-dipiperidine-pyrimidine-[5,4-d]pyrimidine synthetic method. According to the invention, orotic acid is taken as an initial raw material, which iscompletely different with the raw material in the prior art, usage of diethanolamine is omitted, so that an end product as a uniform target product is obtained, the target product is shown as a formula I, and at the same time, the end product yield is increased so that the end product is economic and practical on industrial production.

Synthesis method of dipyridamole intermediate

The invention relates to the technical field of medicine and material intermediates, in particular to a synthesis method of a dipyridamole intermediate. The method is characterized in that pyrimido-[5,4-D]pyrimidine crude products are added into a solvent A; then, a bromination reagent is added; temperature rise is performed till the backflow; reaction is performed for 24 to 48h; after HPLC (HighPerformance Liquid Chromatography) detection display raw materials disappear, reaction stops; aftertreatment and drying are performed to obtain tetrabromo pyrimido-[5,4-D]pyrimidine crude products; (2) the tetrabromo pyrimido-[5,4-D]pyrimidine crude products obtained in the step (1) are added into concentrated hydrochloric acid; heating is performed till the backflow; backflow reaction is maintained for 24 to 36h; the reaction is completed; the temperature is lowered to the room temperature after the reaction stops; aftertreatment and drying are performed to obtain a crude product; after the crude product is recrystallized, drying is performed to obtain the product. The synthesis method has the beneficial effects that the experiment steps are reduced; nitratlon reaction with higher risk and the use of phosphorus pentachloride/phosphorus oxychloride with high toxicity are avoided; the product purity is greater than 98 percent; the total yield is higher than 50 percent; the operation issimple and convenient; the number of three wastes is greatly reduced; the use of strong corrosion and risk reagents is avoided; the safety coefficient is high; the synthesis method is applicable to industrial production.

NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME

The present invention includes pyrimido[5,4-d]pyrimidines that are useful in the prevention and/or treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of preventing and/or treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention.