152460-10-1

Basic information

• Product Name: N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine
• Synonyms: IMatinib IMpurity C;N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine 4-Methyl-3-[4-(3-pyridyl)pyrimidin-2-ylamino]aniline;152460-10-1;N-(5-Amino-2-methyl phenyl)-4-(3- pyridinyl)-2-pyrimidinamine;Imatinib USP Impurity F;RE EXPORT OF N-(5-AMINO-2-METHYLPHENYL)-4-(3-PYPRIDYL)-2-PYRIMIDINE AMINE;1,3-BENZENEDIAMINE,4-METHYL-N3-[4-(3-PYRIDINYL)-2-PYRIMIDINYL]-;6-Methyl-n1-[4-(pyridine-3-yl)pyrimidin-2-yl]benzene-1,3-diamine
• CAS NO: 152460-10-1
• Molecular Formula: C₁₆H₁₅N₅
• Molecular Weight: 277.3238
• EINECS: 1806241-263-5
• Product Categories: Intermediate of Imatinib;Imatinib;Aromatics Compounds;Aromatics;Bases & Related Reagents;Inhibitors;Nucleotides;Heterocycle-Pyrimidine series;intermidiate of Imatinib Methanesulfonate
• Mol File: 152460-10-1.mol
• Article Data: 69

Chemical Properties

• Melting Point: 133-1350C
• Boiling Point: 537.325 °C at 760 mmHg
• Flash Point: 278.765 °C
• Appearance: yellow solid
• Density: 1.266 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.688
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 4.77±0.10(Predicted)
• CAS DataBase Reference: N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine(152460-10-1)
• EPA Substance Registry System: N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine(152460-10-1)

Safety Data

• Hazardous Substances Data: 152460-10-1(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Uses

Different sources of media describe the Uses of 152460-10-1 differently. You can refer to the following data:
1. A selective inhibitor of protein kinase C (PKC).
2. N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine (Imatinib EP Impurity F) is a selective inhibitor of protein kinase C (PKC). It is a COVID19-related research product.

InChI:InChI=1/C16H15N5/c1-11-4-5-13(17)9-15(11)21-16-19-8-6-14(20-16)12-3-2-7-18-10-12/h2-10H,17H2,1H3,(H,19,20,21)

Synthetic route

N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine (152460-09-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethyl acetate for 3h;	100%
With palladium on activated charcoal; hydrogen In ethyl acetate at 20℃; for 3h; Inert atmosphere;	100%
With hydrazine hydrate In N,N-dimethyl-formamide at 100℃; for 3h; Green chemistry;	100%

imatinib (152459-95-5) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With hydrogenchloride; acetic acid at 20℃; Reflux;	97%

tert-butyl (4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)carbamate → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 8h;	95%

(E)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one (55314-16-4, 75415-01-9, 123367-26-0) + (2-methyl-5-aminophenyl)guanidine (581076-64-4) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
In butan-1-ol at 70℃;	92%

2-bromo-4-nitrotoluene (7745-93-9) + 4-pyridin-3-ylpyrimidin-2-ylamine (66521-66-2) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions

Yield

Stage #1: 2-bromo-4-nitrotoluene; 4-pyridin-3-ylpyrimidin-2-ylamine With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 100℃; for 24h; Buchwald-Hartwig Coupling; Inert atmosphere; Stage #2: With potassium tert-butylate; bis(pinacol)diborane In 1,4-dioxane; isopropyl alcohol at 110℃; for 4h; Inert atmosphere; chemoselective reaction;

83%

hydrazine hydrate (7803-57-8) + N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine (152460-09-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With iron(III) chloride; pyrographite In water at 80℃; for 6 - 8h;	80%

(S)-3-allyl-1-benzoyl-4-(4-methoxybenzyl)-3-methylpiperazin-2-one → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water at 20℃; for 1.5h;	75%

4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzoic acid (641569-94-0) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Stage #1: 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid With diphenyl phosphoryl azide; triethylamine In toluene at 100℃; for 12h; Curtius Rearrangement; Stage #2: With hydrogenchloride In water; toluene at 100℃;	60%
Multi-step reaction with 2 steps 1: diphenyl phosphoryl azide; triethylamine / toluene / 12 h / 100 °C 2: trifluoroacetic acid / dichloromethane / 8 h View Scheme

SnCl2.2H2O + N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine (152460-09-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
In hydrogenchloride	46%

methyl-3-pyridylketone (350-03-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / Heating 2: NaOH / propan-2-ol / 24 h / Heating 3: 8.9 g / SnCl2; aq. HCl / 0.5 h View Scheme
Multi-step reaction with 2 steps 1: 92 percent / xylene / 140 °C 2: 92 percent / butan-1-ol / 70 °C View Scheme
Multi-step reaction with 3 steps 2: 41.3 percent / sodium hydroxide / propan-2-ol / 8 h / Heating 3: 60.9 percent / H2 / palladium on charcoal / tetrahydrofuran / 21 h / 750.06 Torr / Ambient temperature View Scheme

3-(N,N-dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one (55314-16-4, 75415-01-9, 123367-26-0) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOH / propan-2-ol / 24 h / Heating 2: 8.9 g / SnCl2; aq. HCl / 0.5 h View Scheme
Multi-step reaction with 2 steps 1: 4-methyl-2-pentanone / 12 h / Reflux 2: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: sodium ethanolate / ethanol / 6 h / 78 °C 1.2: 0.17 h / 78 °C 2.1: sodium hydroxide / water 2.2: 20 °C 3.1: sodium tungstate monohydrate; water; dihydrogen peroxide / acetone / 10 h / 40 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 8 h / 80 °C 5.1: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme

1-(2-methyl-5-nitrophenyl)guanidine nitrate → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOH / propan-2-ol / 24 h / Heating 2: 8.9 g / SnCl2; aq. HCl / 0.5 h View Scheme
Multi-step reaction with 2 steps 1: 41.3 percent / sodium hydroxide / propan-2-ol / 8 h / Heating 2: 60.9 percent / H2 / palladium on charcoal / tetrahydrofuran / 21 h / 750.06 Torr / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: NaOH / propan-2-ol / Heating 2: H2 / 5percent Pd-C / tetrahydrofuran / 750.06 Torr / Ambient temperature View Scheme

2-methyl-5-nitroaniline (99-55-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: HNO3 / ethanol / Heating 2: NaOH / propan-2-ol / 24 h / Heating 3: 8.9 g / SnCl2; aq. HCl / 0.5 h View Scheme
Multi-step reaction with 3 steps 1: aq. HCl / butan-1-ol / 150 °C 2: H2 / Pd/C / butan-1-ol 3: 92 percent / butan-1-ol / 70 °C View Scheme
Multi-step reaction with 4 steps 1.1: nitric acid / ethanol / 25 - 50 °C 1.2: 3 h / Reflux 2.1: sodium hydroxide / water 3.1: 4-methyl-2-pentanone / 12 h / Reflux 4.1: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme

1-(2-methyl-5-nitrophenyl)guanidine (152460-07-6) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / Pd/C / butan-1-ol 2: 92 percent / butan-1-ol / 70 °C View Scheme
Multi-step reaction with 2 steps 1: 4-methyl-2-pentanone / 12 h / Reflux 2: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: acetic acid / 2 h / 90 - 95 °C 1.2: 12 h / Reflux 2.1: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: butan-1-ol / 9 h / 120 °C / Large scale 2: hydrogen / methanol / 45 h / 3102.97 Torr View Scheme
Multi-step reaction with 2 steps 1: butan-1-ol / 9 h / 120 °C 2: hydrogen / methanol / 45 h / 25 °C / 3102.97 Torr View Scheme

(E)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one (55314-16-4, 75415-01-9, 123367-26-0) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 41.3 percent / sodium hydroxide / propan-2-ol / 8 h / Heating 2: 60.9 percent / H2 / palladium on charcoal / tetrahydrofuran / 21 h / 750.06 Torr / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: NaOH / propan-2-ol / Heating 2: H2 / 5percent Pd-C / tetrahydrofuran / 750.06 Torr / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / butan-1-ol / 4 h / 120 °C / Reflux 2: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 15 h / 120 °C / Inert atmosphere; Reflux 3: iron(III) chloride; hydrazine hydrate / methanol / 6 h / 80 °C / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / butan-1-ol / 20 h / Reflux; Inert atmosphere 2: tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; caesium carbonate / 1,4-dioxane / 24 h / 100 °C / Inert atmosphere 3: palladium on carbon; hydrogen / methanol / 760.05 Torr View Scheme
Multi-step reaction with 4 steps 1.1: sodium methylate / ethanol; methanol / 6 h / 78 °C / Inert atmosphere; Molecular sieve 1.2: 0.5 h / 20 °C 2.1: sodium tungstate; dihydrogen peroxide / acetone / 10 h / 40 °C 3.1: triethylamine / 2-methyltetrahydrofuran / 5 h / 20 °C / Inert atmosphere 4.1: 5%-palladium/activated carbon; hydrogen / ethanol / 8 h / 20 °C / 1520.1 Torr View Scheme

palladium (7440-05-3) + N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine (152460-09-8) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
In ethyl acetate
In ethyl acetate

6-chloro-N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidin-amine (1016637-24-3) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With hydrogen; triethylamine; 5%-palladium/activated carbon In ethanol at 20℃; under 3750.38 Torr; for 40h; Product distribution / selectivity;
With hydrogen; triethylamine; 5% Pd(II)/C(eggshell) In ethanol at 20℃; under 3750.38 Torr; for 40h; Autoclave;

1-(5-amino-2-methylphenyl)-3-[3-oxo-3-(3-pyridinyl)-1-prop-1-enyl]guanidine (1026747-16-9) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
With potassium hydroxide In butan-1-ol for 18h; Product distribution / selectivity; Heating / reflux;

β-oxo-3-pyridinepropanal sodium salt (39883-42-6, 41403-76-3) + (2-methyl-5-aminophenyl)guanidine (581076-64-4) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Stage #1: β-oxo-3-pyridinepropanal sodium salt; (2-methyl-5-aminophenyl)guanidine With acetic acid In butan-1-ol at 20℃; for 1h; Inert atmosphere; Stage #2: With potassium hydroxide In butan-1-ol for 18h; Reflux; Inert atmosphere;

(2-methyl-5-nitrophenyl)guanidine nitrate → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / water 2: 4-methyl-2-pentanone / 12 h / Reflux 3: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water 2.1: acetic acid / 2 h / 90 - 95 °C 2.2: 12 h / Reflux 3.1: hydrazine hydrate / palladium 10% on activated carbon / methanol / 8 h / 25 °C / Reflux; Inert atmosphere View Scheme

2-(methylsulfanyl)-4-(3-pyridyl)pyrimidine → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tungstate monohydrate; water; dihydrogen peroxide / acetone / 10 h / 40 °C 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 80 °C 3: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 3 steps 1: sodium tungstate monohydrate; water; dihydrogen peroxide / acetone / 10 h / 40 °C 2: potassium carbonate / N,N-dimethyl-formamide / 80 °C 3: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 3 steps 1: sodium tungstate; dihydrogen peroxide / acetone / 10 h / 40 °C 2: triethylamine / 2-methyltetrahydrofuran / 5 h / 20 °C / Inert atmosphere 3: 5%-palladium/activated carbon; hydrogen / ethanol / 8 h / 20 °C / 1520.1 Torr View Scheme

2-(methylsulfonyl)-4-(pyridin-3-yl)pyrimidine → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 8 h / 80 °C 2: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 80 °C 2: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / 2-methyltetrahydrofuran / 5 h / 20 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / ethanol / 8 h / 20 °C / 1520.1 Torr View Scheme

4-(pyridin-3-yl)pyrimidine-2-thiol → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water 1.2: 20 °C 2.1: sodium tungstate monohydrate; water; dihydrogen peroxide / acetone / 10 h / 40 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 8 h / 80 °C 4.1: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water 1.2: 20 °C 2.1: sodium tungstate monohydrate; water; dihydrogen peroxide / acetone / 10 h / 40 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 80 °C 4.1: iron(III) chloride hexahydrate; hydrazine hydrate / methanol / 6 h / 78 °C View Scheme
Multi-step reaction with 4 steps 1: 0.5 h / 20 °C 2: sodium tungstate; dihydrogen peroxide / acetone / 10 h / 40 °C 3: triethylamine / 2-methyltetrahydrofuran / 5 h / 20 °C / Inert atmosphere 4: 5%-palladium/activated carbon; hydrogen / ethanol / 8 h / 20 °C / 1520.1 Torr View Scheme

2-bromo-4-nitrotoluene (7745-93-9) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 15 h / 120 °C / Inert atmosphere; Reflux 2: iron(III) chloride; hydrazine hydrate / methanol / 6 h / 80 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 20 h / 20 - 100 °C / Inert atmosphere; Schlenk technique 2: hydrazine hydrate; iron(III) chloride; pyrographite / water / 80 °C / Inert atmosphere; Schlenk technique View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium iodide; potassium carbonate / 1,4-dioxane / Inert atmosphere; Reflux 2: ammonium formate; palladium 10% on activated carbon / methanol / 4 h / 30 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; N,N`-dimethylethylenediamine / 1,4-dioxane / 0.5 h / 120 °C / Microwave irradiation 2: zinc; ammonium chloride / tetrahydrofuran / 0.17 h / 80 °C / Microwave irradiation View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 24 h / 120 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / ethyl acetate / Inert atmosphere View Scheme

4-pyridin-3-ylpyrimidin-2-ylamine (66521-66-2) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 15 h / 120 °C / Inert atmosphere; Reflux 2: iron(III) chloride; hydrazine hydrate / methanol / 6 h / 80 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium tert-butylate / dimethyl sulfoxide / 12 h / 120 °C 2: tin(ll) chloride; hydrogenchloride / methanol / 10 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 20 h / 20 - 100 °C / Inert atmosphere; Schlenk technique 2: hydrazine hydrate; iron(III) chloride; pyrographite / water / 80 °C / Inert atmosphere; Schlenk technique View Scheme

3-pyridylboronic acid (1692-25-7) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1-(2,6-diisopropylphenyl)-3-(2-oxo-2-(2,4,6-tri-tert-butylphenylamino)ethyl)-1H-imidazol-3-ium bromide; palladium diacetate; sodium hydroxide / dimethyl sulfoxide; water / 10 h / 100 °C 2: potassium tert-butylate / dimethyl sulfoxide / 12 h / 120 °C 3: tin(ll) chloride; hydrogenchloride / methanol / 10 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran; water / 12 h / 85 °C / Inert atmosphere 2.1: caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: sodium hydroxide; water / ethanol / 5 h / 100 °C 4.1: diphenyl phosphoryl azide; triethylamine / toluene / 12 h / 100 °C 4.2: 100 °C View Scheme
Multi-step reaction with 5 steps 1: caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran; water / 12 h / 85 °C / Inert atmosphere 2: caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 1,4-dioxane / 100 °C / Inert atmosphere 3: sodium hydroxide; water / ethanol / 5 h / 100 °C 4: diphenyl phosphoryl azide; triethylamine / toluene / 12 h / 100 °C 5: trifluoroacetic acid / dichloromethane / 8 h View Scheme

1-methyl-4-nitrobenzene (99-99-0) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine; iron / 1.5 h / 80 °C / Inert atmosphere; Schlenk technique 2: copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine / 1,4-dioxane / 20 h / 20 - 100 °C / Inert atmosphere; Schlenk technique 3: hydrazine hydrate; iron(III) chloride; pyrographite / water / 80 °C / Inert atmosphere; Schlenk technique View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid; N-Bromosuccinimide / water 2: copper(l) iodide; potassium iodide; potassium carbonate / 1,4-dioxane / Inert atmosphere; Reflux 3: ammonium formate; palladium 10% on activated carbon / methanol / 4 h / 30 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: 4-pyridin-3-ylpyrimidin-2-ylamine; iron; bromine / 80 °C 2: copper(l) iodide; N,N`-dimethylethylenediamine / 1,4-dioxane / 0.5 h / 120 °C / Microwave irradiation 3: zinc; ammonium chloride / tetrahydrofuran / 0.17 h / 80 °C / Microwave irradiation View Scheme

N-(4,5-dimethoxy-2-nitrobenzyl)-N-(4-methyl-3-((4-(pyridine-3-yl)pyrimidine-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethyl sulfoxide / 0.17 h / Irradiation 2: hydrogenchloride; acetic acid / 20 °C / Reflux View Scheme

N-(2-methyl-5-nitrophenyl)guanidinium hydrochloride (1207534-99-3) → 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / isopropyl alcohol / 24 h / Reflux 2: hydrogen; platinum(IV) oxide / tetrahydrofuran / 1.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / propan-1-ol / 24 h / Reflux 2: platinum(IV) oxide; hydrogen View Scheme

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) + 3-Iodobenzoic acid (618-51-9) → C23H18IN5O

Conditions	Yield
Stage #1: 3-Iodobenzoic acid With thionyl chloride; N,N-dimethyl-formamide In N,N-dimethyl-formamide at 20℃; for 17h; Stage #2: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 2.5h;	100%

1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → C22H31N5Si2

Conditions	Yield
With hydroxylamine hydrochloride for 5h; Reflux;	99.6%

chloro-trimethyl-silane (75-77-4) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → C22H31N5Si2

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 2h; Solvent;	99.6%

4-((4-methylpiperazin-1-yl)methyl)benzoyl chloride dihydrochloride + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → imatinib (152459-95-5)

Conditions	Yield
Stage #1: 4-((4-methylpiperazin-1-yl)methyl)benzoyl chloride dihydrochloride; 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine In water at 0℃; Stage #2: With sodium hydroxide In water at 50 - 55℃; pH=9 - 9.5; Product distribution / selectivity;	99.26%
With pyridine at 0 - 20℃; for 1h; Product distribution / selectivity;	95%
Stage #1: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With pyridine for 0.333333h; Autoclave; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)benzoyl chloride dihydrochloride at 0 - 25℃; for 8h;	92.7%

trimethylsilyl bromide (2857-97-8) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → C22H31N5Si2

Conditions	Yield
With triethylamine In 2-methyltetrahydrofuran at 0 - 20℃;	99.2%

p-(chloromethyl)benzoyl chloride (876-08-4) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → 4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]-amino}phenyl)benzamide (404844-11-7)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 0 - 20℃; for 4h;	99%
With triethylamine In tetrahydrofuran at 0℃; for 1h; Large scale;	98.1%
With triethylamine In tetrahydrofuran at 0℃; for 4h;	97.4%

p-(chloromethyl)benzoyl chloride (876-08-4) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → 4-(сhloromethyl)-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide hydrochloride (404844-10-6)

Conditions	Yield
In 1,4-dioxane at 22 - 34℃; for 2.75h;	99%

C17H23N4O(1+)*CF3O3S(1-) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → imatinib (152459-95-5)

Conditions	Yield
In N,N-dimethyl-formamide at 40 - 50℃; for 6h; Time;	97.8%

benzoyl chloride (98-88-4) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N-(4-methyl-3(4-(pyridine-3-yl)pyrimidin-2-ylamino)phenyl)benzamide (152459-94-4)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 25℃; for 3h;	97%
With pyridine for 23h; Ambient temperature;	18.3%

phosphonic acid diethyl ester (762-04-9) + 4-dimethylamino-benzaldehyde (100-10-7) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((4-(dimethylamino)phenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.25h; Reagent/catalyst; Microwave irradiation;	96.2%

indole-2,3-dione (91-56-5) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → 3-((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)imino)indolin-2-one

Conditions	Yield
In toluene for 24h; Dean-Stark; Reflux;	96%

4-[(4-methylpiperazin-1-yl)methyl]bromobenzene (368879-17-8) + carbon monoxide (201230-82-2) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → imatinib (152459-95-5)

Conditions	Yield
With palladium diacetate; triethylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 50℃; under 760.051 Torr; for 36h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	95.8%

4-hydroxy-benzaldehyde (123-08-0) + phosphonic acid diethyl ester (762-04-9) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((4-hydroxyphenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.266667h; Microwave irradiation;	95.8%

4-Diethylaminobenzaldehyde (120-21-8) + phosphonic acid diethyl ester (762-04-9) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((4-(diethylamino)phenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.266667h; Microwave irradiation;	95.7%

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N-(5-azido-2-methylphenyl)-4-(pyridine-3-yl)pyrimidin-2-amine (1346617-84-2)

Conditions	Yield
Stage #1: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 1.5h; Stage #2: With sodium azide In water at 0 - 5℃; for 3h;	95%
With fluorosulfonyl azide; potassium hydrogencarbonate In tert-butyl methyl ether; water; N,N-dimethyl-formamide at 20℃; for 0.0833333h;	85%
Stage #1: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With sulfuric acid; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With sodium azide In water at 0 - 20℃; for 3h;	81%
Stage #1: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With hydrogenchloride; sodium nitrite In water at 0℃; for 1h; Stage #2: With sodium azide In water at 0℃; for 2h;
With hydrogenchloride; sodium azide; sodium nitrite In water at 0℃; for 3h;

succinic acid anhydride (108-30-5) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → C20H19N5O3 (1450754-50-3)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;	95%

ammonium thiocyanate (1147550-11-5) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)thiourea

Conditions	Yield
Stage #1: ammonium thiocyanate With benzoyl chloride In acetone for 0.0833333h; Reflux; Stage #2: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine In acetone Reflux;	95%

3,4,5-trimethoxy-benzaldehyde (86-81-7) + phosphonic acid diethyl ester (762-04-9) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((3,4,5-trimethoxyphenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.25h; Microwave irradiation;	94.4%

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) + 3-chlorobenzoate (535-80-8) → 3-chloro-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 1h;	94%

2-[(tert-butoxy)carbonyl]-1 ,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (149353-95-7) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → C31H32N6O3

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 16h;	94%

4-(N,N-Dimethylaminocarbonyl)benzoic acid (34231-49-7) + trifluoroacetic acid (76-05-1) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N1,N1-dimethyl-N4-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzene-1,4-dicarboxamide trifluoroacetate salt

Conditions

Yield

Stage #1: 4-(N,N-Dimethylaminocarbonyl)benzoic acid; 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 50℃; for 1h; Inert atmosphere; Schlenk technique; Stage #2: trifluoroacetic acid In water; acetonitrile

94%

4-chlorobenzaldehyde (104-88-1) + phosphonic acid diethyl ester (762-04-9) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((4-chlorophenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.283333h; Microwave irradiation;	93.8%

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) + 3,5-dinitrobenoyl chloride (99-33-2) → N-[4-methyl-3-(4-pyridin-3-ylpyrimidin-2-ylamino)phenyl]-3,5-dinitrobenzamide (1207534-76-6)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃;	93%

3-nitro-benzaldehyde (99-61-6) + phosphonic acid diethyl ester (762-04-9) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → diethyl ((3-nitrophenyl)((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)methyl)phosphonate

Conditions	Yield
With nickel(II) oxide In neat (no solvent) for 0.3h; Microwave irradiation;	92.6%

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) + 4-((4-methylpiperazin-1-yl)methyl)benzoic acid dihydrochloride → imatinib (152459-95-5)

Conditions	Yield
Stage #1: 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride With pyridine; thionyl chloride at 50 - 60℃; for 3h; Stage #2: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine at -10 - 0℃; for 1h;	92.5%
Stage #1: 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 50℃; for 2h; Stage #2: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine In N,N-dimethyl-formamide at 70℃; for 12h;	91%
Stage #1: 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride With pyridine; thionyl chloride at 20 - 50℃; for 1 - 2h; Stage #2: 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine With pyridine at 0 - 25℃; for 1h; Product distribution / selectivity;	90%

4-nitro-3-(trifluoromethyl)benzoyl chloride (98187-16-7) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N-[4-methyl-3-(4-pyridin-3-ylpyrimidin-2-ylamino)phenyl]-4-nitro-3-trifluoromethylbenzamide (945028-63-7)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃;	92%
With pyridine In dichloromethane at 0℃;
With triethylamine In tetrahydrofuran at 0 - 20℃; for 26h;
With triethylamine In tetrahydrofuran

Upstream product

• 55314-16-4 3-(N,N-dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 
• 152460-08-7 1-(2-methyl-5-nitrophenyl)guanidine nitrate 
• 55314-16-4 (E)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 
• 7440-05-3 palladium 
• 152460-09-8 N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine 
• 39883-42-6 β-oxo-3-pyridinepropanal sodium salt 
• 581076-64-4 (2-methyl-5-aminophenyl)guanidine 
• 637354-24-6 2-(methylsulfanyl)-4-(3-pyridyl)pyrimidine 
• 637354-25-7 2-(methylsulfonyl)-4-(pyridin-3-yl)pyrimidine 
• 1692-25-7 3-pyridylboronic acid 
• 152459-95-5 imatinib 
• 641569-94-0 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid 
• 18595-18-1 3-amino-4-methyl benzoic acid methyl ester 
• 60710-80-7 5-cyano-2-methylaniline 

Downstream Products

• 623900-99-2 4-nitro-N-(4-methyl-3(4-(pyridine-3-yl)pyrimidin-2-ylamino)phenyl)benzamide 
• 641614-84-8 3-iodo-4-(4-methylpiperazin-1-ylmethyl)-N-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}benzamide 
• 152459-95-5 imatinib 

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