4316-98-7

Basic information

• Product Name: 4-AMINO-6-CHLOROPYRIMIDIN-5-YLAMINE
• Synonyms: 4-AMINO-6-CHLOROPYRIMIDIN-5-YLAMINE;4-CHLORO-5,6-DIAMINOPYRIMIDINE;5 6-DIAMINO-4-CHLOROPYRIMIDINE;4,5-Pyrimidinediamine, 6-chloro- (9CI);4-Amino-6-chloropyrimidin-5-ylamine ,97%;6-Chloro-4,5-pyrimidinediamine;6-Chloro-4,5-diaminopyrimidine;6-Chloropyrimidine-4,5-diamine
• CAS NO: 4316-98-7
• Molecular Formula: C₄H₅ClN₄
• Molecular Weight: 144.56
• EINECS: 224-341-1
• Product Categories: PYRIMIDINE;Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycle-Pyrimidine series
• Mol File: 4316-98-7.mol
• Article Data: 18

Chemical Properties

• Melting Point: 252 °C (decomp)
• Boiling Point: 336.7 °C at 760 mmHg
• Flash Point: 157℃
• Appearance: /
• Density: 1.565
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 2.39±0.10(Predicted)
• CAS DataBase Reference: 4-AMINO-6-CHLOROPYRIMIDIN-5-YLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-AMINO-6-CHLOROPYRIMIDIN-5-YLAMINE(4316-98-7)
• EPA Substance Registry System: 4-AMINO-6-CHLOROPYRIMIDIN-5-YLAMINE(4316-98-7)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 4316-98-7(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow solid

Uses

4-Amino-6-chloropyrimidin-5-ylamine is a chlorinated diaminopyrimidine used in the preparation of various bioactive choloropurine derivatives.

InChI:InChI=1/C4H5ClN4/c5-3-2(6)4(7)9-1-8-3/h1H,6H2,(H2,7,8,9)

Synthetic route

5-amino-4,6-dichloropyridimine (5413-85-4) → 6-chloro-4,5-diaminopyrimidine (4316-98-7)

Conditions	Yield
With ammonia In water at 100℃; for 46h;	97%
With ammonia at 100℃; for 46h;	97%
With ammonia In water at 100℃; for 46h;	97%

6-chloro-5-nitropyrimidin-4-amine (4316-94-3) → 6-chloro-4,5-diaminopyrimidine (4316-98-7)

Conditions	Yield
With tin(ll) chloride In ethanol for 1h; Heating;	67%
With methanol; nickel Hydrogenation;
With water; zinc
With water; iron; hydrogenchloride In ethanol at 85℃; Industry scale;

4,5-diamino-6-hydroxypyrimidine (1672-50-0) → 6-chloro-4,5-diaminopyrimidine (4316-98-7)

Conditions	Yield
With N,N-dimethyl-aniline; trichlorophosphate for 4h; Heating / reflux;	15%

9-(1-Ethoxyethyl-1)-6-chloropurine (33441-77-9) → 6-chloro-4,5-diaminopyrimidine (4316-98-7) + 9-(1-ethoxyethyl)hypoxanthine

Conditions	Yield
With sodium hydroxide In water at 50.1℃; Product distribution; Rate constant; other temperatures; alkalyne hydrolysis of 6-substituted 9-(1-ethoxyethyl)purines, effect of substituent, formation of intermediates;

(2R,3S,4S)-5-[(Z)-5-Amino-6-chloro-pyrimidin-4-ylimino]-pentane-1,2,3,4-tetraol → 6-chloro-4,5-diaminopyrimidine (4316-98-7) + D-ribose (50-69-1)

Conditions	Yield
With sodium hydroxide at 50.1℃; Mechanism; Rate constant; hydroxide concentration influence;

6-chloro-4,5-diaminopyrimidine (4316-98-7) → 6-iodopyrimidine-4,5-diamine (655255-14-4)

Conditions	Yield
With hydrogen iodide In water at 0 - 20℃; for 24.5h;	98%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 1,1'-carbonyldiimidazole (530-62-1) → 6-chloro-7H-purin-8(9H)-one (37527-48-3)

Conditions	Yield
In 1,4-dioxane for 0.833333h; Reflux; Inert atmosphere;	96%
In 1,4-dioxane for 48h; Heating / reflux;	86%
In 1,4-dioxane for 48h; Heating / reflux;	86%
In 1,4-dioxane for 48h; Heating / reflux;	86%
In 1,4-dioxane for 48h; Heating / reflux;

6-chloro-4,5-diaminopyrimidine (4316-98-7) + benzoic acid (65-85-0) → 6-chloro-8-phenyl-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Reagent/catalyst; Solvent; Temperature; Green chemistry;	94%
With ammonium chloride; trichlorophosphate at 100℃; for 18h;	69%
With ammonium chloride; trichlorophosphate at 100℃; for 24h;

formic acid (64-18-6) + 6-chloro-4,5-diaminopyrimidine (4316-98-7) → N-(5-amino-6-chloropyrimidin-4-yl)formamide (7501-32-8)

Conditions	Yield
With acetic anhydride at 70℃; for 72h; Inert atmosphere;	94%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 9-Anthracenecarboxylic acid (723-62-6) → 6-chloro-8-(anthracen-9-yl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	94%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 4-Bromobenzoic acid (586-76-5) → 6-chloro-8-(4-bromophenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	93%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 4-hydroxy-benzoic acid (99-96-7) → 6-chloro-8-(4-hydroxyphenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	93%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 2,5-dihydroxybenzoic acid. (490-79-9) → 6-chloro-8-(2,5-dihydroxyphenyl)-9H-purine

Conditions	Yield
In ethanol at 20℃; for 1h; Green chemistry;	92%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 4-trifluoromethylbenzoic acid (455-24-3) → 6-chloro-8-(4-(trifluoromethyl)phenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	91%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 2-bromobenzoic-acid (88-65-3) → 6-chloro-8-(2-bromophenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	91%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + ortho-chlorobenzoic acid (118-91-2) → 6-chloro-8-(2-chlorophenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	90%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 3,4-Dihydroxybenzoic acid (99-50-3) → 6-chloro-8-(3,4-dihydroxyphenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	90%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + benzaldehyde (100-52-7) → 8-phenyl-1,7-dihydro-purine-6-thione (3298-76-8)

Conditions	Yield
With sulfur In N,N-dimethyl-formamide at 90 - 100℃;	89%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 4-methoxybenzoic acid (100-09-4) → 6-chloro-8-(4-methoxyphenyl)-9H-purine

Conditions	Yield
With Ag/SiO2 catalyst In ethanol at 20℃; for 1h; Green chemistry;	89%

ortho-methylbenzoic acid (118-90-1) + 6-chloro-4,5-diaminopyrimidine (4316-98-7) → 6-chloro-8-(o-tolyl)-7H-purine

Conditions	Yield
With ammonium chloride; trichlorophosphate at 110℃;	88.4%
With ammonium chloride; trichlorophosphate at 110℃;	88.4%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + Cyclobutanecarboxylic acid (3721-95-7) → 6-chloro-8-cyclobutyl-9H-purine

Conditions	Yield
With ammonium chloride; trichlorophosphate at 110℃; for 16h;	86%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 1-naphthalenecarboxylic acid (86-55-5) → 6-chloro-8-(1-naphthyl)-9H-purine (1007125-12-3)

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine; 1-naphthalenecarboxylic acid With trichlorophosphate at 110℃; for 5.5h; Stage #2: With sodium hydrogencarbonate In dichloromethane; water	80%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + N,N-dimethyl acetamide (127-19-5) → N'-(4-amino-6-chloropyrimidin-5-yl)-N,N-dimethylacetamidine

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine; N,N-dimethyl acetamide at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With trichlorophosphate at 25℃; for 2h;	80%
Stage #1: 6-chloro-4,5-diaminopyrimidine; N,N-dimethyl acetamide at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With trichlorophosphate at 20℃; for 2h;	80%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + (E)-3-phenylacrylic acid (140-10-3) + 4-amino-phenol (123-30-8) → (E)-8-styryl-N-(4-hydroxyphenyl)-9H-purin-6-amine

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine; (E)-3-phenylacrylic acid With ammonium chloride; trichlorophosphate for 24h; Reflux; Stage #2: 4-amino-phenol With hydrogenchloride In isopropyl alcohol Reflux;	79.2%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + 3,4-dimethoxy-trans-cinnamic acid (14737-89-4) → (E)-6-chloro-8-(3,4-dimethoxystyryl)-9H-purine

Conditions	Yield
With ammonium chloride; trichlorophosphate for 24h; Reflux;	78.5%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + salicylaldehyde (90-02-8) → 5-Oxa-2,4,11-triaza-dibenzo[a,d]cyclohepten-1-ylamine (84762-59-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 110 - 120℃; for 4h;	78%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + di(succinimido) carbonate (74124-79-1) → 6-chloro-7H-purin-8(9H)-one (37527-48-3)

Conditions	Yield
In acetonitrile for 16h; Heating / reflux;	78%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + methyl 2,2,2-trimethoxyacetate (18370-95-1) → 4-chloro-6-methoxypteridin-7(8H)-one (1365604-90-5)

Conditions	Yield
camphor-10-sulfonic acid In acetonitrile for 16h; Reflux;	76%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + (E)-3-phenylacrylic acid (140-10-3) + o-toluidine (95-53-4) → (E)-8-styryl-N-(o-tolyl)-9H-purin-6-amine

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine; (E)-3-phenylacrylic acid With ammonium chloride; trichlorophosphate for 24h; Reflux; Stage #2: o-toluidine With hydrogenchloride In isopropyl alcohol Reflux;	72.3%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + dimethylglyoxal (431-03-8) → 6,7-dimethyl-4-hydroxypteridine (14684-54-9)

Conditions	Yield
In methanol; toluene for 1h; Reflux;	72%
In methanol; toluene for 1h; Reflux;	72%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + trifluoroacetic acid (76-05-1) → 6-hydroxy-8-trifluoromethyl purine

Conditions	Yield
at 70℃; for 16h;	61%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → N'-(4-amino-6-chloropyrimidin-5-yl)-N,N-dimethylformamidine

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine; N,N-dimethyl-formamide at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With trichlorophosphate at 25℃; for 2h;	60%
Stage #1: 6-chloro-4,5-diaminopyrimidine; N,N-dimethyl-formamide at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With trichlorophosphate at 20℃; for 2h;	60%

6-chloro-4,5-diaminopyrimidine (4316-98-7) + isopropyl alcohol (67-63-0) → 7-isopropoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine

Conditions	Yield
Stage #1: 6-chloro-4,5-diaminopyrimidine With n-Amyl nitrite In 1,4-dioxane at 80 - 90℃; for 0.5h; Stage #2: isopropyl alcohol With sodium at 80℃; for 0.5h;	55%

Upstream product

• 4316-94-3 6-chloro-5-nitropyrimidin-4-amine 
• 1672-50-0 4,5-diamino-6-hydroxypyrimidine 
• 33441-77-9 9-(1-Ethoxyethyl-1)-6-chloropurine 
• 5413-85-4 5-amino-4,6-dichloropyridimine 

Downstream Products

• 64194-58-7 6-amino-5-formylamino-3H-pyrimidin-4-one 
• 68-94-0 1,7-dihydro-6H-purin-6-one 
• 72700-48-2 4-chloro-pteridine 
• 87-42-3 6-chloro-7H-purine 
• 2268-13-5 8-trifluoromethyl-1,7-dihydro-purin-6-one 
• 13754-19-3 4,5-pyrimidinediamine 
• 2683-90-1 8-azahypoxanthine 
• 17861-06-2 6-ethoxy-9H-purine 
• 57500-07-9 6-benzyloxypurine 
• 92001-53-1 6-chloro-8-ethyl-9H-purine 
• 92001-52-0 6-chloro-8-methyl-9H-purine 
• 37527-48-3 8-hydroxy-6-chloroadenine 

Relevant articles and documents

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INHIBITORS OF PI3K-DELTA AND METHODS OF THEIR USE AND MANUFACTURE

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

Scale-up of organic reactions in a pharmaceutical kilo-lab using a commercial microwave reactor

A range of pharmaceutically relevant reactions were investigated for scale-up in a kilo-lab environment using a commercial batch microwave reactor. Typical scale-up issues are discussed, taking into account the specific limitations of microwave heating in large-scale experiments. Examples of scale-up from 15 mL to 1 L are presented and demonstrate that the synthesis of compounds on greater than 100 g scale is feasible in one batch. Aided by this new technology reaction times have been significantly reduced and the productivity of our scale-up laboratory has been enhanced. Production rates of several hundred grams per day were achieved using microwave technology. The article concludes with a brief discussion of advantages and disadvantages of this type of batch microwave reactor.