3993-78-0

Basic information

• Product Name: 2-Amino-4-chloropyrimidine
• Synonyms: AKOS BBS-00005838;4-CHLOROPYRIMIDIN-2-AMINE;2-PYRIMIDINAMINE, 4-CHLORO-;2-AMINO-4-CHLOROPYRIMIDINE;CHLORO-ISO-CYTOSINE;2-Pyrimidinamine, 4-chloro- (9CI);2-AMINO-4-CHLOROPYRIMIDINE, 98+%;2-amine-4-chloropyrimidine
• CAS NO: 3993-78-0
• Molecular Formula: C₄H₄ClN₃
• Molecular Weight: 129.55
• Product Categories: PYRIMIDINE;APIs & Intermediate;Pyridines, Pyrimidines, Purines and Pteredines;Amines;Pyrazines, Pyrimidines & Pyridazines;Heterocyclic Compounds;Bases & Related Reagents;Heterocycles;Nucleotides;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Pyrimidines;PyrimidinesHeterocyclic Building Blocks;Heterocycle-Pyrimidine series;chloropyrimidin
• Mol File: 3993-78-0.mol
• Article Data: 18

Chemical Properties

• Melting Point: 155-160 °C (dec.)
• Boiling Point: 314.609 °C at 760 mmHg
• Flash Point: 144.07 °C
• Appearance: White solid
• Density: 1.437g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.618
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Soluble in dimethyl sulfoxide.
• PKA: 3.55±0.10(Predicted)
• CAS DataBase Reference: 2-Amino-4-chloropyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-4-chloropyrimidine(3993-78-0)
• EPA Substance Registry System: 2-Amino-4-chloropyrimidine(3993-78-0)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-41-37/38-22
• Safety Statements: 26-36/37/39-36/39-60
• WGK Germany: 3
• Hazardous Substances Data: 3993-78-0(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 3993-78-0 differently. You can refer to the following data:
1. 2-Amino-4-chloropyrimidine is a substrate used in a palladium-catalyzed cyanation with zinc(II) cyanide. It is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff fields.
2. Substrate used in a palladium-catalyzed cyanation with zinc(II) cyanide.

Purification Methods

It has also been purified by sublimation in a vacuum and recrystrallisation from H2O. [Hilbert & Johnson J Am Chem Soc 52 1155 1930, Beilstein 24 H 80, 25 III/IV 2117.]

InChI:InChI=1/C4H4ClN3/c5-3-1-2-7-4(6)8-3/h1-2H,(H2,6,7,8)

Synthetic route

4-chloro-2-methanesulfonylpyrimidine (97229-11-3) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With aq. NH3 In isopropyl alcohol	100%

2-amino-4-hydroxypyrimidine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With pyridine; trichlorophosphate at 180℃; under 150.015 - 900.09 Torr; for 2h; Neat (no solvent);	95%
With trichlorophosphate for 1.5h; Heating;	52%

isocytosine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
Stage #1: isocytosine With chlorosulfonic acid; trichlorophosphate at 20 - 95℃; Inert atmosphere; Stage #2: With ammonium hydroxide In water at 20℃; pH=~ 7; Cooling wit ice;	92%
Stage #1: isocytosine With trichlorophosphate for 1.5h; Reflux; Stage #2: With sodium carbonate In water pH=9; Cooling with ice;	52%

isocytosine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With chlorosulfonic acid; trichlorophosphate at -5 - 90℃; for 5h; Inert atmosphere;	73%

2,6-Dichloropyrimidine (3934-20-1) → 2-chloropyrimidin-4-amine (7461-50-9) + 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonium hydroxide In water at 20℃;	A 69% B 23%
With ammonium hydroxide at 20℃; for 5h;	A 59% B 37%
With ammonium hydroxide In water at 20℃; for 5h;	A 59% B 37%

2,6-Dichloropyrimidine (3934-20-1) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonia; water
With ammonium hydroxide at 20℃; for 16h;

2-amino-3H-pyrimidin-2-one → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With sulfuric acid; trichlorophosphate
With chlorosulphuric acid; trichlorophosphate

4-oxy-2-amino-pyrimidine → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With trichlorophosphate

2,6-Dichloropyrimidine (3934-20-1) + ammonia (7664-41-7) → 2-chloropyrimidin-4-amine (7461-50-9) + 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
at 100℃;

2-nitro-3H-4-chloropyrimidine → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonia	51.3 g

2-amino-4-chloropyrimidine (3993-78-0) + cyclopropanemethylamine (2516-47-4) → N4-(cyclopropylmethyl)pyrimidine-2,4-diamine (1169699-05-1)

Conditions	Yield
In ethanol at 100℃; for 16h;	100%

tert-butyl (1S)-2-(3-aminophenoxy)-1-(1H-indol-3-ylmethyl)ethylcarbamate (552330-61-7) + 2-amino-4-chloropyrimidine (3993-78-0) → tert-butyl (1S)-2-{3-[(2-aminopyrimidin-4-yl)amino]phenoxy}-1-(1H-indol-3-ylmethyl)ethylcarbamate

Conditions	Yield
In ethanol	98%
In ethanol at 80℃; for 13h;	98%

(4-cyano-3-fluorophenyl)boronic acid (843663-18-3) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(2-amino-4-pyrimidinyl)-2-fluorobenzonitrile (1238077-12-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane; water at 95℃; for 3h; Suzuki Coupling; Inert atmosphere;	97%
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane; water at 95℃; for 3h; Suzuki coupling; Inert atmosphere;	83%

morpholine (110-91-8) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-morpholin-4-ylpyrimidin-2-ylamine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 4h; Reflux;	95%
With N-ethyl-N,N-diisopropylamine In acetonitrile for 4h; Reflux;	95%
With potassium carbonate In dimethyl sulfoxide at 100℃; for 0.333333h; Microwave irradiation;	93%

2-amino-4-chloropyrimidine (3993-78-0) → 2-amino-4-iodopyrimidine (815610-16-3)

Conditions	Yield
With hydrogen iodide In water at 0 - 20℃; for 3h;	95%
With hydrogen iodide; sodium iodide In water at 20℃; for 3.5h;	86%

2-amino-4-chloropyrimidine (3993-78-0) + 3-chloro-aniline (108-42-9) → N4-(3-chlorophenyl)pyrimidine-2,4-diamine

Conditions	Yield
With hydrogenchloride for 2h; Heating;	94%

2-amino-4-chloropyrimidine (3993-78-0) + amino-4 hydroxy-2 toluene (2835-95-2) → 5-(2-aminopyrimidin-4-ylamino)-2-methylphenol (933045-98-8)

Conditions	Yield
Stage #1: 2-amino-4-chloropyrimidine; amino-4 hydroxy-2 toluene With hydrogenchloride In ethanol; water at 90℃; for 18h; Stage #2: With potassium carbonate In ethanol; water; ethyl acetate Product distribution / selectivity;	94%
With hydrogenchloride In ethanol; water at 80 - 90℃; Product distribution / selectivity;

2-amino-4-chloropyrimidine (3993-78-0) + 6-bromo-5-methoxy-1H-indole (106103-36-0) → 4-(6-bromo-5-methoxy-1H-indol-1-yl)pyrimidin-2-amine

Conditions	Yield
Stage #1: 6-bromo-5-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 15℃; for 0.5h; Stage #2: 2-amino-4-chloropyrimidine In N,N-dimethyl-formamide; mineral oil at 80℃; for 18h;	94%

(4-(4-chloro-3-(trifluoromethyl)phenoxy)phenyl)methanol (1369257-58-8) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-((4-(4-chloro-3-(trifluoromethyl)phenoxy)benzyl)oxy)pyrimidin-2-amine

Conditions	Yield
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃;	93%

2-amino-4-chloropyrimidine (3993-78-0) + m-nitrobenzene boronic acid (13331-27-6) → 4-(3-nitrophenyl)-2-aminopyrimidine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane at 95℃; Inert atmosphere;	93%

2-amino-4-chloropyrimidine (3993-78-0) → 4-hydrazinylpyrimidin-2-amine (33575-09-6)

Conditions	Yield
With hydrazine hydrate In ethanol at 80 - 100℃; Microwave irradiation;	93%

2-amino-4-chloropyrimidine (3993-78-0) + 5-methoxy-4-aza-1H-indole (17288-40-3) → 4-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-1-yl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 2h;	92.13%

2-amino-4-chloropyrimidine (3993-78-0) + sodium methylate (124-41-4) → 4-methoxypyrimidin-2-amine (155-90-8)

Conditions	Yield
In methanol at 20℃; for 24h;	92%
With methanol
In methanol at 50℃; for 2.5h;

4-chloro-2-methanesulfonylpyrimidine (97229-11-3) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With aq. NH3 In isopropyl alcohol	100%

2-amino-4-hydroxypyrimidine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With pyridine; trichlorophosphate at 180℃; under 150.015 - 900.09 Torr; for 2h; Neat (no solvent);	95%
With trichlorophosphate for 1.5h; Heating;	52%

isocytosine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
Stage #1: isocytosine With chlorosulfonic acid; trichlorophosphate at 20 - 95℃; Inert atmosphere; Stage #2: With ammonium hydroxide In water at 20℃; pH=~ 7; Cooling wit ice;	92%
Stage #1: isocytosine With trichlorophosphate for 1.5h; Reflux; Stage #2: With sodium carbonate In water pH=9; Cooling with ice;	52%

isocytosine (108-53-2) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With chlorosulfonic acid; trichlorophosphate at -5 - 90℃; for 5h; Inert atmosphere;	73%

2,6-Dichloropyrimidine (3934-20-1) → 2-chloropyrimidin-4-amine (7461-50-9) + 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonium hydroxide In water at 20℃;	A 69% B 23%
With ammonium hydroxide at 20℃; for 5h;	A 59% B 37%
With ammonium hydroxide In water at 20℃; for 5h;	A 59% B 37%

2,6-Dichloropyrimidine (3934-20-1) → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonia; water
With ammonium hydroxide at 20℃; for 16h;

2-amino-3H-pyrimidin-2-one → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With sulfuric acid; trichlorophosphate
With chlorosulphuric acid; trichlorophosphate

4-oxy-2-amino-pyrimidine → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With trichlorophosphate

2,6-Dichloropyrimidine (3934-20-1) + ammonia (7664-41-7) → 2-chloropyrimidin-4-amine (7461-50-9) + 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
at 100℃;

2-nitro-3H-4-chloropyrimidine → 2-amino-4-chloropyrimidine (3993-78-0)

Conditions	Yield
With ammonia	51.3 g

2-amino-4-chloropyrimidine (3993-78-0) + cyclopropanemethylamine (2516-47-4) → N4-(cyclopropylmethyl)pyrimidine-2,4-diamine (1169699-05-1)

Conditions	Yield
In ethanol at 100℃; for 16h;	100%

tert-butyl (1S)-2-(3-aminophenoxy)-1-(1H-indol-3-ylmethyl)ethylcarbamate (552330-61-7) + 2-amino-4-chloropyrimidine (3993-78-0) → tert-butyl (1S)-2-{3-[(2-aminopyrimidin-4-yl)amino]phenoxy}-1-(1H-indol-3-ylmethyl)ethylcarbamate

Conditions	Yield
In ethanol	98%
In ethanol at 80℃; for 13h;	98%

(4-cyano-3-fluorophenyl)boronic acid (843663-18-3) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(2-amino-4-pyrimidinyl)-2-fluorobenzonitrile (1238077-12-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane; water at 95℃; for 3h; Suzuki Coupling; Inert atmosphere;	97%
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane; water at 95℃; for 3h; Suzuki coupling; Inert atmosphere;	83%

morpholine (110-91-8) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-morpholin-4-ylpyrimidin-2-ylamine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 4h; Reflux;	95%
With N-ethyl-N,N-diisopropylamine In acetonitrile for 4h; Reflux;	95%
With potassium carbonate In dimethyl sulfoxide at 100℃; for 0.333333h; Microwave irradiation;	93%

2-amino-4-chloropyrimidine (3993-78-0) → 2-amino-4-iodopyrimidine (815610-16-3)

Conditions	Yield
With hydrogen iodide In water at 0 - 20℃; for 3h;	95%
With hydrogen iodide; sodium iodide In water at 20℃; for 3.5h;	86%

2-amino-4-chloropyrimidine (3993-78-0) + 3-chloro-aniline (108-42-9) → N4-(3-chlorophenyl)pyrimidine-2,4-diamine

Conditions	Yield
With hydrogenchloride for 2h; Heating;	94%

2-amino-4-chloropyrimidine (3993-78-0) + amino-4 hydroxy-2 toluene (2835-95-2) → 5-(2-aminopyrimidin-4-ylamino)-2-methylphenol (933045-98-8)

Conditions	Yield
Stage #1: 2-amino-4-chloropyrimidine; amino-4 hydroxy-2 toluene With hydrogenchloride In ethanol; water at 90℃; for 18h; Stage #2: With potassium carbonate In ethanol; water; ethyl acetate Product distribution / selectivity;	94%
With hydrogenchloride In ethanol; water at 80 - 90℃; Product distribution / selectivity;

2-amino-4-chloropyrimidine (3993-78-0) + 6-bromo-5-methoxy-1H-indole (106103-36-0) → 4-(6-bromo-5-methoxy-1H-indol-1-yl)pyrimidin-2-amine

Conditions	Yield
Stage #1: 6-bromo-5-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 15℃; for 0.5h; Stage #2: 2-amino-4-chloropyrimidine In N,N-dimethyl-formamide; mineral oil at 80℃; for 18h;	94%

(4-(4-chloro-3-(trifluoromethyl)phenoxy)phenyl)methanol (1369257-58-8) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-((4-(4-chloro-3-(trifluoromethyl)phenoxy)benzyl)oxy)pyrimidin-2-amine

Conditions	Yield
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃;	93%

2-amino-4-chloropyrimidine (3993-78-0) + m-nitrobenzene boronic acid (13331-27-6) → 4-(3-nitrophenyl)-2-aminopyrimidine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane at 95℃; Inert atmosphere;	93%

2-amino-4-chloropyrimidine (3993-78-0) → 4-hydrazinylpyrimidin-2-amine (33575-09-6)

Conditions	Yield
With hydrazine hydrate In ethanol at 80 - 100℃; Microwave irradiation;	93%

2-amino-4-chloropyrimidine (3993-78-0) + 5-methoxy-4-aza-1H-indole (17288-40-3) → 4-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-1-yl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 2h;	92.13%

2-amino-4-chloropyrimidine (3993-78-0) + sodium methylate (124-41-4) → 4-methoxypyrimidin-2-amine (155-90-8)

Conditions	Yield
In methanol at 20℃; for 24h;	92%
With methanol
In methanol at 50℃; for 2.5h;

2-amino-4-chloropyrimidine (3993-78-0) + 6-bromo-indoline (63839-24-7) → 4-(6-bromoindolin-1-yl)pyrimidin-2-amine (1202765-50-1)

Conditions	Yield
In 1,4-dioxane at 90℃; for 21h;	92%
With hydrogenchloride In water at 60℃;	80%

2-amino-4-chloropyrimidine (3993-78-0) + N-benzylpiperidine-3-carboxamide → 1-(2-aminopyrimidin-4-yl)-N-benzylpiperidine-3-carboxamide

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 120℃; for 18h; Sealed tube;	92%

C7H6IN3 (1208228-61-8) + 2-amino-4-chloropyrimidine (3993-78-0) → C11H9IN6 (953411-13-7)

Conditions	Yield
In ethanol at 80℃; for 2.5h;	91%

2-amino-4-chloropyrimidine (3993-78-0) + (2-fluoro-pyridin-3-yl)boronic acid (174669-73-9) → 4-(2-fluoropyridin-3-yl)pyrimidin-2-amine

Conditions	Yield
With bis(di-tert-butylphenylphosphine)palladium(II) dichloride; potassium acetate In water; acetonitrile at 85℃; for 15h; Sealed tube; Inert atmosphere;	91%

pyrrolidine (123-75-1) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(pyrrolidin-1-yl)pyrimidin-2-amine (1215986-09-6)

Conditions	Yield
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 20 - 120℃; Inert atmosphere;	89.7%
at 150℃; for 1h; Microwave irradiation;	67%
at 150℃; for 1h; Microwave irradiation; Sealed tube;	67%

1-indoline (496-15-1) + 2-amino-4-chloropyrimidine (3993-78-0) + isopropyl alcohol (67-63-0) → 2-amino-4-(indolin-1-yl)pyrimidine (1401661-20-8)

Conditions	Yield
With potassium hydroxide In 1,4-dioxane; water	89.6%

2-amino-4-chloropyrimidine (3993-78-0) + 2-(5-fluorofuran-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 4-(5-fluorofuran-2-yl)pyrimidine-2-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere;	89.01%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 90℃; for 2h; Inert atmosphere;	89.01%

1-methyl-piperazine (109-01-3) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine

Conditions	Yield
In ethanol at 150℃; for 0.166667h; Microwave irradiation; Sealed tube;	89%
at 120℃; for 0.166667h; Microwave irradiation;	54%

6-bromo-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran] (1202765-56-7) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(6-bromo-2',3',5',6'-tetrahydrospiro[indole-3,4'-pyran]-1(2H)-yl)pyrimidin-2-amine (1202765-64-7)

Conditions	Yield
Stage #1: 6-bromo-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]; 2-amino-4-chloropyrimidine With hydrogenchloride In water at 60℃; for 17.5h; Stage #2: With sodium hydroxide In water Cooling;	88.3%

2-[4-(4-amino-2-fluoro-phenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanol (867018-12-0) + 2-amino-4-chloropyrimidine (3993-78-0) → 2-(4-{4-[(2-aminopyrimidin-4-yl)amino]-2-fluorophenoxy}-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanol

Conditions	Yield
Stage #1: 2-[4-(4-amino-2-fluoro-phenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanol; 2-amino-4-chloropyrimidine With hydrogenchloride In water Heating / reflux; Stage #2: With sodium hydroxide In water pH=10;	88%

2-amino-4-chloropyrimidine (3993-78-0) + C11H12N2S → N4-((4-methyl-2-phenyl-5-thiazolyl)methyl)pyrimidine-2,4-diamine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 40℃; for 3h; Inert atmosphere;	88%

tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (942070-45-3) + 2-amino-4-chloropyrimidine (3993-78-0) → 4-(1H-indol-3-yl)pyrimidin-2-amine (289628-76-8)

Conditions	Yield
With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); caesium carbonate In water; isopropyl alcohol at 80℃; for 16h; Suzuki-Miyaura Coupling; Inert atmosphere; Schlenk technique;	87%
With caesium carbonate In methanol at 100℃; for 24h; Suzuki coupling; Inert atmosphere;	73%

2-amino-4-chloropyrimidine (3993-78-0) + 2-Methoxyphenylboronic acid (5720-06-9) → 4-(2-methoxyphenyl)pyrimidin-2-amine (915070-01-8)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 100℃; for 2h; Inert atmosphere;	87%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 95℃; for 2h; Suzuki-Miyaura Coupling; Inert atmosphere;	86%

2-amino-4-chloropyrimidine (3993-78-0) → 2-amino-5-bromo-4-chloropyrimidine (1044767-99-8)

Conditions	Yield
With bromine; acetic acid at 20℃; for 2h;	86%
With N-Bromosuccinimide In chloroform at 20℃;	62%
With N-Bromosuccinimide In methanol; acetonitrile at 20℃; for 0.5h;

Upstream product

• 108-53-2 2-amino-4-hydroxypyrimidine 
• 108-53-2 isocytosine 
• 108-53-2 isocytosine 
• 97229-11-3 4-chloro-2-methanesulfonylpyrimidine 
• 3934-20-1 2,6-Dichloropyrimidine 
• 7664-41-7 ammonia 

Downstream Products

• 289503-27-1 2-amino-4-(N-tosyl-6'-bromo-3'-indolyl)pyrimidine 
• 1064721-17-0 (1S)-[2-{5-[3-(2-amino-pyrimidin-4-ylamino)-phenyl]-pyridin-3-yloxy}-1-(1H-indol-3-ylmethyl)-ethyl]-carbamic acid tert-butyl ester 
• 924644-04-2 4-(4-aminopyrimidin-2-yl)-piperazine-1-carboxylic acid benzyl ester 
• 924644-05-3 4-(2-aminopyrimidin-4-yl)-piperazine-1-carboxylic acid benzyl ester 
• 1227362-02-8 6-(2-aminopyrimidin-4-yl)-2-(2-(dimethylamino)ethyl)-3-(3-methoxybenzyl)quinazolin-4(3H)-one 
• 1228020-08-3 4-(4-Methyl-3-phenylquinolin-2-ylmethoxy)pyrimidin-2-ylamine formate salt 
• 1219727-06-6 1-(4-(2-aminopyrimidin-4-yl)phenyl)-3-(3-methoxybenzyl)urea 
• 1161759-39-2 C₂₁H₂₀N₄O₄ 
• 1296885-69-2 C₁₂H₉Cl₂N₃O 
• 155-90-8 4-methoxypyrimidin-2-amine 
• 199865-36-6 3-(2-aminopyrimidin-4-yl)-1-methyl-1H-indole 
• 1394119-31-3 4-(6-iodo-1H-indazol-1-yl)pyrimidin-2-amine 
• 1394119-32-4 4-(6-iodo-2H-indazol-2-yl)pyrimidin-2-amine 
• 1374239-34-5 1-{(S)-3-[(2-aminopyrimidin-4-yl)methylamino]piperidin-1-yl}-2-(3,5-dichlorophenylamino)ethanone 

Relevant articles and documents

Preparation method for osimertinib mesylate

The invention discloses a preparation method for osimertinib mesylate. The chemical name of osimertinib mesylate is N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)amino)phenyl)acrylamide mesylate (AZD9291), and the chemical formula is C28H33N7O2.CH4O3S. The process of the preparation technique of the preparation method is simple, materials areeasy to obtain, and the preparation method is cost-efficient and environment-friendly, can help realize industrialization, can promote the economic and technological development of osimertinib activeingredients, reduces production cost, and is suitable for mass production.

Synthesis and functional characterization of imbutamine analogs as histamine H3 and H4 receptor ligands

Imbutamine (4-(1H-imidazol-4-yl)butanamine) is a potent histamine H 3 (H3R) and H4 receptor (H4R) agonist (EC50 values: 3 and 66 nM, respectively). Aiming at improved selectivity for the H4R, the imidazole ring in imbutamine was methyl-substituted or replaced by various differently substituted heterocycles (1,2,3-triazoles, 1,2,4-triazoles, pyridines, pyrimidines) as potential bioisosteres. Investigations in [35S]GTPγS binding assays using membranes of Sf9 insect cells expressing the respective human histamine receptor subtype revealed only very weak activity of most of the synthesized hetarylalkylamines at both receptors. By contrast, the introduction of substituents at the 4-imidazolyl ring was most effective regarding H 4R selectivity. This holds for methyl substitution in position 2 and, especially, in position 5. 5-Methylimbutamine (H4R: EC50 = 59 nM, α = 0.8) was equipotent with imbutamine at the hH4R, but revealed about 16-fold selectivity for the hH4R compared to the hH3R (EC50 980 nM, α = 0.36), whereas imbutamine preferred the hH3R. The functional activities were in agreement with radioligand binding data. The results support the hypothesis that, by analogy with histamine, methyl substitution in histamine homologs offers a way to shift the selectivity in favor of the H4R. According to a bioisosteric approach, the imidazole ring in the dual histamine H3/H4 receptor agonist imbutamine (n = 4) was replaced by various five- and six-membered N-heterocycles. Whereas these structural modifications resulted in a reduction or loss of activity at both receptors, 5-methyl substitution at the imidazol-4-yl ring in imbutamine changed the receptor subtype selectivity in favor of the H4R.

Highly efficient, chemoselective syntheses of 2-methoxy-4-substituted pyrimidines

Three 2-methoxy-4-substituted pyrimidine compounds were chemoselectively synthesized by diazotization, using 2,4-dichloropyrimidine as the starting material. In nonaqueous diazotization reaction system, halo-substituted 6 and 7 were efficiently prepared, and in aqueous medium, hydrolysis product 8 was afforded.