10320-42-0

Usage

Chemical Properties

Light yellow solid

InChI:InChI=1/C4H2ClN3O2/c5-4-6-1-3(2-7-4)8(9)10/h1-2H

Synthetic route

2-hydroxy-5-nitropyrimidine (3264-10-6) → 2-Chloro-5-nitropyrimidine (10320-42-0)

Conditions	Yield
With trichlorophosphate for 0.5h; Heating;	97%
With N,N-dimethyl-aniline; trichlorophosphate for 2h; Heating / reflux;	54%

tert.-butylnitrite (540-80-7) + 5-nitropyrimidin-2-amine (3073-77-6) + copper(II) chloride (7447-39-4) → 2-Chloro-5-nitropyrimidine (10320-42-0)

Conditions	Yield
With magnesium sulfate In diethyl ether; acetonitrile	50%

5-nitropyrimidin-2-amine (3073-77-6) → 2-Chloro-5-nitropyrimidine (10320-42-0)

Conditions	Yield
With magnesium sulphate; tert.-butylnitrite; copper dichloride In acetonitrile at 65 - 80℃; for 0.5h;	50%

5-nitro-2(1H)-pyrimidinone (3264-10-6) → 2-Chloro-5-nitropyrimidine (10320-42-0)

Conditions	Yield
With trichlorophosphate

2-Chloro-5-nitropyrimidine (10320-42-0) + ethylene glycol (107-21-1) → 2-((5-nitropyrimidin-2-yl)oxy)ethanol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 80℃; for 0.333333h;	100%
With N-ethyl-N,N-diisopropylamine at 80℃; for 0.333333h;	100%

2-Chloro-5-nitropyrimidine (10320-42-0) → 2-((5-nitropyrimidin-2-yl)oxy)ethanol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethylene glycol at 80℃; for 0.333333h;	100%

2-Chloro-5-nitropyrimidine (10320-42-0) + sodium thiomethoxide (5188-07-8) → 2-(methylthio)-5-nitropyrimidine (14001-70-8)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	99%

Thiomorpholin (123-90-0) + 2-Chloro-5-nitropyrimidine (10320-42-0) → 4-(5-nitropyrimidin-2-yl)thiomorpholine (1562399-15-8)

Conditions	Yield
Stage #1: Thiomorpholin; 2-Chloro-5-nitropyrimidine In tetrahydrofuran; acetonitrile for 0.166667h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water; acetonitrile at 20℃; for 0.75h; Inert atmosphere;	99%

2-Chloro-5-nitropyrimidine (10320-42-0) → 2-chloro-5-aminopyrimidine (56621-90-0)

Conditions	Yield
With ethanol; iron; acetic acid for 6h; Reflux;	98%
With iron; acetic acid at 75℃; for 2h;	98%
With iron; acetic acid In ethanol; water at 70℃;	85%

2-Chloro-5-nitropyrimidine (10320-42-0) + N-(4-chloro-2,6-difluorophenyl)-7-(2-oxopyrrolidin-1-yl)-2,3-dihydro-1H-indole-5-sulfonamide → N-(4-chloro-2,6-difluorophenyl)-1-(5-nitropyrimidin-2-yl)-7-(2-oxopyrrolidin-1-yl)-2,3-dihydro-1H-indole-5-sulfonamide

Conditions	Yield
In tetrahydrofuran Reflux;	98%

2-Chloro-5-nitropyrimidine (10320-42-0) + aniline (62-53-3) → (5-nitro-pyrimidin-2-yl)-phenyl-amine (26806-61-1)

Conditions	Yield
In acetonitrile Inert atmosphere;	97%
With potassium carbonate In water; acetonitrile at 20℃; for 3h;
In acetonitrile at 20℃; for 4h; Inert atmosphere;

2-Chloro-5-nitropyrimidine (10320-42-0) + 1-amino-3-methylbenzene (108-44-1) → 5-nitro-N-(m-tolyl)pyrimidin-2-amine

Conditions	Yield
In acetonitrile Inert atmosphere;	97%
In acetonitrile at 20℃; for 4h; Inert atmosphere;

2-Chloro-5-nitropyrimidine (10320-42-0) + 2-Fluoroaniline (348-54-9) → N-(2-fluorophenyl)-5-nitropyrimidin-2-amine

Conditions	Yield
Inert atmosphere;	97%
In acetonitrile at 20℃; for 4h; Inert atmosphere;

2-Chloro-5-nitropyrimidine (10320-42-0) → 5-nitropyrimidin-2-amine (3073-77-6)

Conditions	Yield
With ammonium hydroxide In tetrahydrofuran at 20℃; for 1h;	96%

morpholine (110-91-8) + 2-Chloro-5-nitropyrimidine (10320-42-0) → 4-(5-nitropyrimidin-2-yl)morpholine (65735-66-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 72h;	95%
Stage #1: morpholine With triethylamine In tetrahydrofuran for 0.25h; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran at 27℃; for 12h;	86%
In acetonitrile at 20℃; for 3h;	61%
In tetrahydrofuran for 2h; Reflux;

2-Chloro-5-nitropyrimidine (10320-42-0) + 3-methyl-phenol (108-39-4) → 5-nitro-2-(m-tolyloxy)pyrimidine

Conditions	Yield
Stage #1: 3-methyl-phenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	95%

3,4-Dimethylphenol (95-65-8) + 2-Chloro-5-nitropyrimidine (10320-42-0) → 2-(3,4-dimethylphenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 3,4-Dimethylphenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	95%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-fluoroaniline (371-40-4) → N-(4-fluorophenyl)-5-nitropyrimidin-2-amine

Conditions	Yield
In acetonitrile Inert atmosphere;	95%
In acetonitrile at 20℃; for 4h; Inert atmosphere;

pyrrolidine (123-75-1) + 2-Chloro-5-nitropyrimidine (10320-42-0) → 5-nitro-2-(pyrrolidin-1-yl)pyrimidine (873090-71-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5h;	94%

2-Chloro-5-nitropyrimidine (10320-42-0) + piperazine-1-sulfonic acid dimethylamide (98961-97-8) → N,N-dimethyl-4-(5-nitropyrimidin-2-yl)piperazine-1-sulfonamide (1146543-74-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 24h;	92%
With triethylamine In tetrahydrofuran at 20℃; for 24h;	92%

2-Chloro-5-nitropyrimidine (10320-42-0) + N-(4-chloro-2,6-difluorophenyl)-7-(2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indole-5-sulfonamide → N-(4-chloro-2,6-difluorophenyl)-1-(5-nitropyrimidin-2-yl)-7-(2-oxoimidazolidin-1-yl)-2,3-dihydro-1H-indole-5-sulfonamide

Conditions	Yield
In tetrahydrofuran Reflux;	92%

1-methyl-piperazine (109-01-3) + 2-Chloro-5-nitropyrimidine (10320-42-0) → 2-(4-methylpiperazin-1-yl)-5-nitropyrimidine (943749-60-8)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃;	91%
Stage #1: 1-methyl-piperazine With triethylamine In tetrahydrofuran for 0.25h; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran at 27℃; for 12h;	83%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-bromo-phenol (106-41-2) → 2-(4-bromophenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 4-bromo-phenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%
With triethylamine In tetrahydrofuran at 20℃; for 3h;	294 mg

2-Chloro-5-nitropyrimidine (10320-42-0) + phenol (108-95-2) → 5-nitro-2-phenoxypyrimidine

Conditions	Yield
Stage #1: phenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	6.55 g
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	6.55 g

2-Chloro-5-nitropyrimidine (10320-42-0) + para-tert-butylphenol (98-54-4) → 2-(4-(tert-butyl)phenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: para-tert-butylphenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + 2,4-Xylenol (105-67-9) → 2-(2,4-dimethylphenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 2,4-Xylenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-methoxy-phenol (150-76-5) → 2-(4-methoxyphenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 4-methoxy-phenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-Fluorophenol (371-41-5) → 2-(4-fluorophenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 4-Fluorophenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-chloro-phenol (106-48-9) → 2-(4-chlorophenoxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: 4-chloro-phenol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + 4-Hydroxyacetophenone (99-93-4) → 1-(4-((5-nitropyrimidin-2-yl)oxy)phenyl)ethane-1-one

Conditions	Yield
Stage #1: 4-Hydroxyacetophenone With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + o-hydroxyacetophenone (118-93-4) → 1-(2-((5-nitropyrimidin-2-yl)oxy)phenyl)ethane-1-one

Conditions	Yield
Stage #1: o-hydroxyacetophenone With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + α-naphthol (90-15-3) → 2-(naphthalen-1-yloxy)-5-nitropyrimidine

Conditions	Yield
Stage #1: α-naphthol With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: 2-Chloro-5-nitropyrimidine In tetrahydrofuran; mineral oil at 50℃; for 12h;	90%

2-Chloro-5-nitropyrimidine (10320-42-0) + o-toluidine (95-53-4) → 5-nitro-N-(o-tolyl)pyrimidin-2-amine

Conditions	Yield
In acetonitrile for 5h; Inert atmosphere;	90%
In acetonitrile at 20℃; for 4h; Inert atmosphere;

Upstream product

• 3264-10-6 5-nitro-2(1H)-pyrimidinone 
• 3264-10-6 2-hydroxy-5-nitropyrimidine 
• 3073-77-6 5-nitropyrimidin-2-amine 
• 540-80-7 tert.-butylnitrite 
• 7447-39-4 copper(II) chloride 

Downstream Products

• 14001-69-5 5-nitro-2-methoxypyrimidine 
• 56621-90-0 2-chloro-5-aminopyrimidine 
• 1450-76-6 1-(2-hydroxy-5-nitrophenyl)ethanone 
• 88626-94-2 5-nitro-2-(diacetylmethyl)pyrimidine 
• 77696-49-2 5-nitro-2-(2,2-diphenylhydrazino)pyrimidine 
• 949558-55-8 1-(4-methoxybenzyl)-3-methyl-4-(5-nitropyrimidin-2-yloxy)-1H-pyrazolo[3,4-b]pyridine 
• 65735-66-2 4-(5-nitropyrimidin-2-yl)morpholine 
• 14001-70-8 2-(methylthio)-5-nitropyrimidine 
• 959160-55-5 5-cyclohexyl-3-isopropyl-8-methyl-1-(5-nitropyrimidin-2-yl)-1H-1,3,4-benzotriazepin-2(3H)-one 
• 3073-77-6 5-nitropyrimidin-2-amine 
• 1431727-37-5 tert-butyl (3-((5-nitropyrimidin-2-yl)amino)phenyl)carbamate 
• 26806-61-1 (5-nitro-pyrimidin-2-yl)-phenyl-amine 
• 26806-63-3 (5-nitro-pyrimidin-2-yl)-(3-trifluoromethyl-phenyl)-amine 
• 1630970-04-5 C₁₁H₁₀N₄O₃ 

Relevant academic research and scientific papers

N -pyridyl and pyrimidine benzamides as KCNQ2/Q3 potassium channel openers for the treatment of epilepsy

A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro- benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.

BENZOTRIAZEPINONE DERIVATIVES

The present invention is concerned with benzotriazepinone derivatives, their intermediates, uses thereof and processes for their production. In particular, the present invention relates to parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrp) receptor ligands, (PTH-1 or PTH/PTHrp receptor ligands). The invention also relates to methods of preparing such ligands and to compounds which are useful as intermediates in such methods.

Pyrimidines as novel openers of potassium ion channels

The present invention provides a genus of pyrimidine amides that are useful as openers of potassium ion channels. The compounds of the invention are of use in both therapeutic and diagnostic methods.

THE SYNTHESIS AND SOME REACTIONS OF CHLOROPYRIMIDINES

Several chloro-hydroxy- and amino- chloropyrimidines have been prepared.The chloro groups have been replaced by hydrogen, mercapto, or hydroxyamino substituents to give useful synthetic intermediates.