6972-27-6

Usage

Uses

Used in Pharmaceutical Industry:
6-Chloro-1,3-dimethyl-2,4-(1H,3H)-pyrimidinedione is used as a key intermediate in the synthesis of various substituted uracils and their derivatives for the development of nucleic acid analogs and other bioactive molecules. These analogs have potential applications in the treatment of various diseases, including viral infections and cancer, due to their ability to modulate the structure and function of nucleic acids.
Used in Chemical Research:
6-Chloro-1,3-dimethyl-2,4-(1H,3H)-pyrimidinedione is also used as a research compound in the field of organic chemistry. It serves as a valuable building block for the synthesis of various complex organic molecules and can be used to study the reactivity and properties of substituted pyrimidinediones.
Used in Biochemical Applications:
6-Chloro-1,3-dimethyl-2,4-(1H,3H)-pyrimidinedione can be used in the development of novel nucleic acid analogs with modified properties, such as increased stability, altered binding affinity, or enhanced biological activity. These analogs can be employed in various biochemical applications, including the development of new therapeutic agents, diagnostic tools, and research reagents.

InChI:InChI=1/C6H7ClN2O2/c1-8-4(7)3-5(10)9(2)6(8)11/h3H,1-2H3

Synthetic route

1,3-dimethylbarbituric acid (769-42-6) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
With water; trichlorophosphate Heating;	93%
With water; trichlorophosphate for 6h; Reflux; Large scale;	92.3%
With trichlorophosphate

6-chlorouracil (4270-27-3) + methyl bromide (74-83-9) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
With sodium hydroxide; tetrabutylammomium bromide In dichloromethane at 20℃; for 48h;	90%

methyl bromide (74-83-9) + 3-methyl-6-chlorouracil (4318-56-3) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
With sodium hydroxide; tetrabutylammomium bromide In dichloromethane; water at 40℃; Alkylation;	90%

edaravone (89-25-8) + 6-chloro-5-formyl-1,3-dimethyluracil (35824-85-2) → 1,3-Dimethyl-6-chlorouracil (6972-27-6) + 1-phenyl-3-methyl-4-(1-phenyl-3-methyl-5-oxo-4-pyrazolylidene)methylene-5-pyrazolone (4702-90-3)

Conditions	Yield
With piperidine In ethanol at 20℃; for 0.5h;	A 75% B n/a

6-chlorouracil (4270-27-3) + methyl iodide (74-88-4) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 23℃; for 3h; Schlenk technique; Inert atmosphere;	52%

6-chloro-2,4-dimethoxypyrimidine (6320-15-6) + methyl iodide (74-88-4) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
at 90℃;

6-Amino-1,3-dimethylbarbituric acid (6642-31-5) → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous HCl 2: POCl3 View Scheme

6-chlorouracil (4270-27-3) + methyl halide → 1,3-Dimethyl-6-chlorouracil (6972-27-6)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 70℃; for 3h;

methanol (67-56-1) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 6-methoxy-1,3-dimethyluracil (4097-20-5)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2h; Ambient temperature;	100%

propan-1-ol (71-23-8) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 1,3-Dimethyl-6-propoxy-1H-pyrimidine-2,4-dione (93767-18-1)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2h; Ambient temperature;	100%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + ethanol (64-17-5) → 1,3-dimethyl-6-ethoxyuracil (93787-99-6)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2h; Ambient temperature;	100%
With sodium carbonate for 28h; Reflux;	96%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + pentan-1-ol (71-41-0) → 1,3-Dimethyl-6-pentyloxy-1H-pyrimidine-2,4-dione (93767-19-2)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2h; Ambient temperature;	100%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + allyl alcohol (107-18-6) → 1,3-dimethyluracil-6-allyl ether (93767-20-5)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 1.5h; Ambient temperature;	100%
With sodium for 2h; Heating;	63.3%
With sodium at 30 - 40℃; for 0.5h;	57.2%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + ethanethiol (75-08-1) → 6-Ethylsulfanyl-1,3-dimethyl-1H-pyrimidine-2,4-dione (35218-96-3)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2.5h; Ambient temperature;	100%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + benzyl alcohol (100-51-6) → 6-Benzyloxy-1,3-dimethyl-1H-pyrimidine-2,4-dione (93767-21-6)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water for 2h; Ambient temperature;	100%

naphthalene (91-20-3) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 6-methoxy-1,3-dimethyluracil (4097-20-5)

Conditions	Yield
In methanol at 20℃; for 1h; UV-irradiation;	100%

2,3-Dimethyl-2-butene (563-79-1) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 1,1,2,2,3,5-hexamethyl-1,2-dihydrocyclobutapyrimidine-4,6(3H,5H)-dione (82959-62-4)

Conditions	Yield
In acetone Irradiation;	99%
In acetone at 20℃; for 2h; Cycloaddition; Photolysis;

piperidine (110-89-4) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 1,3-dimethyl-6-(piperidin-1-yl)pyrimidine-2,4(1H,3H)-dione

Conditions	Yield
at 60℃; for 0.00833333h; microwave irradiation;	99%
In 1,4-dioxane at 100℃; for 2h;	98%
In dichloromethane for 1h; Ambient temperature;	85%
In water Heating;	59%
Stage #1: 1,3-Dimethyl-6-chlorouracil With (1,3,5-triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate; palladium diacetate In N,N-dimethyl-formamide for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: piperidine With triethylamine In N,N-dimethyl-formamide at 23℃; for 2h; Schlenk technique; Inert atmosphere;	168 mg

1,3-Dimethyl-6-chlorouracil (6972-27-6) + sodium methylate (124-41-4) → 6-methoxy-1,3-dimethyluracil (4097-20-5)

Conditions	Yield
In methanol at 60℃; for 0.00833333h; microwave irradiation;	99%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + aniline (62-53-3) → 6-anilino-1,3-dimethyluracil (7278-51-5)

Conditions	Yield
at 160℃; for 0.5h; microwave irradiation;	98%
In neat (no solvent) at 180℃; for 3h;	87%
In ethanol for 12h; Heating;	80%

1,3-Dimethyl-6-chlorouracil (6972-27-6) → 6-chloro-1,3-dimethyl-5-nitrouracil (1203-25-4)

Conditions	Yield
With sulfuric acid; potassium nitrate 1.) 15 min, 7 deg C, 2.) 30 min, 20 deg C;	98%
With sulfuric acid; nitric acid at 5℃;
With nitric acid; sulfuric acid at 10℃; for 2h;

1,3-Dimethyl-6-chlorouracil (6972-27-6) + benzylamine (100-46-9) → 6-(benzylamino)-1,3-dimethyluracil (5770-49-0)

Conditions	Yield
at 130℃; for 0.05h; microwave irradiation;	98%
With triethylamine In 1,4-dioxane for 10h; Reflux;	87%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + sodium ethanolate (141-52-6) → 1,3-dimethyl-6-ethoxyuracil (93787-99-6)

Conditions	Yield
In ethanol at 60℃; for 0.00833333h; microwave irradiation;	97%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + 4-bromo-aniline (106-40-1) → 6-(4-bromo-anilino)-1,3-dimethyl-1H-pyrimidine-2,4-dione (64663-99-6)

Conditions	Yield
In neat (no solvent) at 180℃; for 3h;	97%
at 180℃; for 3h;	70%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + N-butylamine (109-73-9) → 6-n-butylamino-1,3-dimethyluracil (5770-46-7)

Conditions	Yield
In N,N-dimethyl-formamide for 18h; Reflux;	96%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + methylamine (74-89-5) → 1,3-dimethyl-6-methylamino-1H-pyrimidine-2,4-dione (5770-42-3)

Conditions	Yield
In methanol for 16h; Large scale;	95%
With water
In water

N-methylpropargylamine (35161-71-8) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 1,3-dimethyl-6-(N-methyl-N-propargyl)aminouracil (94154-86-6)

Conditions	Yield
	95%
for 6h; Ambient temperature;	87.7%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + benzyl-methyl-amine (103-67-3) → 1,3-dimethyl-6-(benzylmethylamino)uracil

Conditions	Yield
at 130℃; for 0.0166667h; microwave irradiation;	94%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + 2-phenyl-4,4,5,5-tetramethyl-1,3,2-dioxoborole (24388-23-6) → 1,3-dimethyl-6-phenyluracil (42542-99-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 16h; Suzuki-Miyaura coupling; Reflux;	94%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + sodium thiophenolate (930-69-8) → 1,3-dimethyl-6-phenylthiouracil (35218-98-5)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 60℃; for 0.00833333h; microwave irradiation;	93%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + methyl 2-(11-(3-(piperazin-1-yl)propylidene)-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetate (943783-06-0) → methyl 2-(11-(3-(4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)piperazin-1-yl)propylidene)-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetate (943781-13-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 80℃; for 7h;	93%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + 1-(2,4-dichlorophenyl)oxy-4-chloro-but-2-yne (68536-76-5) → 6-[4-(2,4-dichloro-phenoxy)-but-2-ynylsulfanyl]-1,3-dimethyl-1H-pyrimidine-2,4-dione (897935-82-9)

Conditions	Yield
Stage #1: 1,3-Dimethyl-6-chlorouracil With sodium hydrogensulfide In ethanol at 0℃; for 6h; Stage #2: 1-(2,4-dichlorophenyl)oxy-4-chloro-but-2-yne With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dichloromethane; water at 20℃; for 12h;	92%

N-(2-bromo-5-methoxybenzyl),N-methylamine (767289-08-7) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → 6-((2-bromo-5-methoxybenzyl)(methyl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (1148107-95-2)

Conditions	Yield
In ethanol Reflux;	92%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + 4-methoxy-aniline (104-94-9) → 6-p-Methoxyphenylamino-1,3-dimethyluracil (58137-44-3)

Conditions	Yield
In neat (no solvent) at 180℃; for 3h;	91%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + 2-chloro-4-iodoaniline (42016-93-3) → C12H11ClIN3O2 (1026989-89-8)

Conditions	Yield
Stage #1: 1,3-Dimethyl-6-chlorouracil; 2-chloro-4-iodoaniline With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 5℃; for 0.833333h; Stage #2: With water; ammonium chloride In tetrahydrofuran	91%

1,3-Dimethyl-6-chlorouracil (6972-27-6) + p,p'-diaminobiphenyl (92-87-5) → 6,6'-[biphenyl-4,4'-diyldi(imino)]bis(1,3-dimethylpyrimidine-2,4(1H,3H)-dione) (1448799-77-6)

Conditions	Yield
With quinoline at 180℃; for 3h;	91%

pyrrolidine (123-75-1) + 1,3-Dimethyl-6-chlorouracil (6972-27-6) → N,N-dimethyl-6-pyrrolidino uracil (74151-85-2)

Conditions	Yield
In dichloromethane for 1h; Ambient temperature;	90%
In ethanol Ambient temperature;

Upstream product

• 6320-15-6 6-chloro-2,4-dimethoxypyrimidine 
• 74-88-4 methyl iodide 
• 769-42-6 1,3-dimethylbarbituric acid 
• 4270-27-3 6-chlorouracil 
• 74-83-9 methyl bromide 
• 4318-56-3 3-methyl-6-chlorouracil 
• 89-25-8 edaravone 
• 35824-85-2 6-chloro-5-formyl-1,3-dimethyluracil 
• 6642-31-5 6-Amino-1,3-dimethylbarbituric acid 

Downstream Products

• 5770-43-4 6-ethylamino-1,3-dimethyl-1H-pyrimidine-2,4-dione 
• 5770-44-5 6-(2-hydroxyethylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dion 
• 13177-82-7 1,3-dimethyl-6-dimethylaminouracil 
• 5770-46-7 6-n-butylamino-1,3-dimethyluracil 
• 7278-51-5 6-anilino-1,3-dimethyluracil 
• 5770-42-3 1,3-dimethyl-6-methylamino-1H-pyrimidine-2,4-dione 
• 874-14-6 1,3-dimethyluracil 
• 51369-91-6 1,3-dimethyl-6-(3-phenyl-oxiranyl)-1H-pyrimidine-2,4-dione 
• 3120-45-4 3.3.5.7-Tetramethyl-6.8-dioxo-5.6.7.8-tetrahydro-3H-pyrimido<5.4-c>-1.2.5-oxadiazin 
• 144104-81-4 3-(2,6-Dichloro-phenyl)-5,7-dimethyl-7H-isoxazolo[5,4-d]pyrimidine-4,6-dione 
• 35221-08-0 1,7-Dihydro-5,7-dimethyl-3-phenyl-4H-pyrazolo<3,4-d>pyrimidin-4,6(5H)-dion 
• 75029-42-4 5-Benzoyl-6-chlor-1,3-dimethyluracilbenzoylhydrazon 
• 78790-70-2 1,3-dimethyl-5-(2-amino-5-methoxyphenyl)-6-aminouracil 
• 7269-96-7 6-(4-chloro-anilino)-1,3-dimethyl-1H-pyrimidine-2,4-dione 

Relevant academic research and scientific papers

Doxofylline impurity and preparation method thereof

The invention provides a doxofylline impurity and a preparation method thereof. The impurity is 9-(2,2-dimethoxyethyl)-1,3-dimethyl-1H-purine-2,6(3H,9H)-diketone. A compound provided by the inventioncan be used as a standard substance for detecting ingredients of a doxofylline finished product, thereby improving the accurate positioning and characterization of the detection and analysis of doxofylline finished product for the impurities, strengthening the control of the impurities, and further improving the quality of the doxofylline finished products.

Iodine/persulfate-promoted site-selective direct thiolation of quinolones and uracils

A simple and general method for direct thiolation of 4-quinolones with disulfides or thiols under I2/K2S2O8 system has been developed. Under the optimal conditions, the C–S bond coupling can take place effectively with good to decent yields and excellent regioselectivity of the S-linked products. The established metal-free site-selective approach was also applicable to transform a range of uracil substrates to the thio-substituted products under mild conditions. Further transformation to the sulfone derivatives can be conveniently performed in one-pot. These easy-to-handle protocols represent a useful and interesting synthetic alternative with good substrate scope and functional group compatibility.

Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes

A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields.

A natural product four methyl uric acid fully synthetic method

The invention relates to a total synthesis method for a natural product tetramethyl uric acid. The method comprises the following steps: (1) using 1,3-dimethyl barbituric acid as a raw material for synthesis to obtain an intermediate 6-substitued-1,3-dimethyl pyrimidine-2,4-diketone; (2) synthesizing an intermediate 1,3-dimethyl-6-methylamino pyrimidine-2,4-diketone; (3) synthesizing an intermediate 1,3-dimethyl-5-substitued-6-methylamino pyrimidine-2,4-diketone; (4) synthesizing an intermediate 1,3-dimethyl-5,6-dimethylamino pyrimidine-2,4-diketone; (5) synthesizing a target compound 1,3,7,9-tetramethyl uric acid. The method is convenient for synthesis, has a higher yield, and can ease the demand on tetramethyl products to a certain degree.

ETHYNYLXANTHINES, PREPARATION AND USE AS CALCIUM ION CHANNEL MODULATORS

The present invention relates to novel pharmaceutical compounds, which exhibit ability to act as calcium ion channel modulators, methods for their synthesis and the treatment and/or prevention of various diseases and disorders including deregulated calcium ion channel activity.

AMIDES OF 2-AMINO-4-ARYLTHIAZOLE COMPOUNDS AND THEIR SALTS

The present disclosure is directed to salts of N-{4-[2,4-difluoro-3- (trifluoromethyl)phenyl]-1,3-thiazol-2-yl}-2-(1,3-dimethyl-2,4-dioxo-1,2,3,4- tetrahydrothieno[2,3- d]pyrimidin-5-yl)acetamide and process for the preparation thereof (formula II)..

AMIDES OF HETEROCYCLIC COMPOUNDS AS TRPA1 INHIBITORS

Amides of heterocyclic compounds as Transient Receptor Potential subfamily A (TRPA) modulators are provided In particular, compounds described herein are useful for treating or preventing diseases, conditions and/ or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1) Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1. (I).

Enantioconservative synthesis of polysubstituted pyrimido[4,5- b ]azepines

A three-step enantioconservative protocol was developed for the synthesis of polysubstituted pyrimido[4,5-b]azepines. First, 1,3-dimethyl-6-[N-(2- alkoxycarbonylalkyl)amino]uracils were synthesized by nucleophilic substitution of 6-chloro-1,3-dimethyluracil with amino acids. Subsequent acylation of the uracils by a mixture of acetic anhydride and cyanoacetic acid gave the corresponding 5-cyanoacetylated pyrimidines. In the final step, the pyrimidines were subjected to Dieckmann cyclization with a sodium alcoholate in the corresponding alcohol to afford the corresponding pyrimido[4,5-b]azepines. By using uracils of N-monosubstituted amino acids, cyclization was combined with ring opening of the pyrimidine ring system to afford polysubstituted azepines. Georg Thieme Verlag Stuttgart.

FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS

The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPAl (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPAl. Formula (I)

PYRIMIDINEDIONE-FUSED HETEROCYCLIC COMPOUNDS AS TRPA1 MODULATORS

The present invention is related to novel pyrimidinedione-fused heterocyclic compounds as TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.