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CAS No. : | 1005-37-4 | MDL No. : | MFCD02091108 |
Formula : | C5H7ClN4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CXWJDRREGHIEMH-UHFFFAOYSA-N |
M.W : | 158.59 | Pubchem ID : | 235446 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.2 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 40.75 |
TPSA : | 63.83 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.47 cm/s |
Log Po/w (iLOGP) : | 1.29 |
Log Po/w (XLOGP3) : | 1.13 |
Log Po/w (WLOGP) : | 0.57 |
Log Po/w (MLOGP) : | 0.16 |
Log Po/w (SILICOS-IT) : | 0.54 |
Consensus Log Po/w : | 0.74 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.91 |
Solubility : | 1.94 mg/ml ; 0.0122 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.06 |
Solubility : | 1.37 mg/ml ; 0.00863 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.34 |
Solubility : | 0.732 mg/ml ; 0.00461 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.91 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H317-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With N-ethyl-N,N-diisopropylamine In methanol; butan-1-ol at 95℃; | Intermediate 20 -chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine. A mixture of 4,6-dichloropyrimidin-2-amine (3.28 g, 20.0 mmol), methanamine (12.0 mL, 24.0 mmol; as a 2 M solution in methanol) and Hunig's base in n- butanol (20 mL) was heated at 95°C overnight. The mixture was concentrated and the crude was taken up in EtOAc (300 mL) and washed with water (3 x 150 mL). The organic layer was dried over MgS04, filtered and concentrated to give the desired product as a buff solid (2.90 g, 91 percent). LCMS [M+H]+ 159. |
90.6% | at 80℃; for 6 h; Sealed tube | 2-Amino-4,6-dichloropyrimidine (1.0 g, 6.1 mmol) was dissolved in 15 mL of methylamine solution.The tube was sealed at 80 ° C for 6 h.Dry the solvent,Ethyl acetate dissolved,Column chromatography purification [P: E = 4: 1 (V: V)],Obtained white solid 0.87g,The yield was 90.6percent. |
85% | With potassium carbonate In ethanol for 18 h; Heating / reflux | 2-Amino-4-chloro-6-methylayninopyrimidine (NU6042) (for Use as an Intermediate Compound) A mixture of 2-amino-4,6-dichloropyrimidine (1 g, 6.1 mmol), methylamine (0.8 ml), potassium carbonate (0.5 g, 3.62 mmol) and anhydrous ethanol (15 ml) were heated under reflux, under nitrogen, for 18 h. The reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated to a volume of approximately 2 ml, when a cream solid was obtained (0.82 g, 85percent), m.p. 152-157° C.; νmax/cm-1 3442 (NH), 2934 (CH3), 2549 (NH2); δH (200 MHz, d6-DMSO) 3.48 (3H, s, CH3), 5.84 (1H, s, C(5)H), 6.53 (2H, br s, NH2), 7.28 (1H, br s, NH); m/z (+EI) 158 (M+, 100percent), 123 (M+-Cl, 9), 94 (18). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With N-ethyl-N,N-diisopropylamine; In methanol; butan-1-ol; at 95℃; | Intermediate 20 -chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine. A mixture of 4,6-dichloropyrimidin-2-amine (3.28 g, 20.0 mmol), methanamine (12.0 mL, 24.0 mmol; as a 2 M solution in methanol) and Hunig's base in n- butanol (20 mL) was heated at 95C overnight. The mixture was concentrated and the crude was taken up in EtOAc (300 mL) and washed with water (3 x 150 mL). The organic layer was dried over MgS04, filtered and concentrated to give the desired product as a buff solid (2.90 g, 91 %). LCMS [M+H]+ 159. |
90.6% | at 80℃; for 6h;Sealed tube; | 2-Amino-4,6-dichloropyrimidine (1.0 g, 6.1 mmol) was dissolved in 15 mL of methylamine solution.The tube was sealed at 80 C for 6 h.Dry the solvent,Ethyl acetate dissolved,Column chromatography purification [P: E = 4: 1 (V: V)],Obtained white solid 0.87g,The yield was 90.6%. |
85% | With potassium carbonate; In ethanol; for 18h;Heating / reflux; | 2-Amino-4-chloro-6-methylayninopyrimidine (NU6042) (for Use as an Intermediate Compound) A mixture of 2-amino-4,6-dichloropyrimidine (1 g, 6.1 mmol), methylamine (0.8 ml), potassium carbonate (0.5 g, 3.62 mmol) and anhydrous ethanol (15 ml) were heated under reflux, under nitrogen, for 18 h. The reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated to a volume of approximately 2 ml, when a cream solid was obtained (0.82 g, 85%), m.p. 152-157 C.; numax/cm-1 3442 (NH), 2934 (CH3), 2549 (NH2); deltaH (200 MHz, d6-DMSO) 3.48 (3H, s, CH3), 5.84 (1H, s, C(5)H), 6.53 (2H, br s, NH2), 7.28 (1H, br s, NH); m/z (+EI) 158 (M+, 100%), 123 (M+-Cl, 9), 94 (18). |
In methanol; at 50℃; for 2h; | To 2-amino-4,6-dichloropyrimidine (1.0 g, 6.1 mmol) in CH3OH (20 ml.) was added methylamine (2.37 g, 24.4 mmol, 32% solution of methylamine in CH3OH), and the reaction mixture was stirred for 2 hours at 50 0C. The mixture was concentrated, and the resulting solid was partitioned between EtOAc and water. The organic layer was separated, dried (Na2SO4), filtered, and concentrated to afford the title compound (833 mg) as a pale yellow solid. LC-MS (ES) m/z = 159, 161 [M+H]+. | |
In ethanol; water; at 70℃; for 4h; | 2-Amino-4-anilino-6-methylaminopyrimidine was synthesized, via 2-amino-4-chloro-6-methylaminopyrimidine, with 2-amino-4,6-dichloropyrimidine as a starting material. 2-Amino-4,6-dichloropyrimidine (32.8 g), a 40% aqueous methylamine solution (34.5 mL), and ethanol (300 mL) were mixed, followed by stirring at an internal temperature of 70 C. for 4 hours. Subsequently, the solvent was concentrated under reduced pressure, and crystallization from acetonitrile was performed. The product was collected by filtration and was used without purification for the subsequent step. The crude product of 2-amino-4-chloro-6-methylaminopyrimidine, aniline (27.4 mL), methoxyethanol (100 mL), and hydrochloric acid (0.2 mL) were mixed, followed by stirring with heating at 120 C. for 3 hours. After cooling, the reaction solution was added to sodium bicarbonate water (500 mL)/ethyl acetate under ice cooling to extract the product with ethyl acetate. After concentration, purification by column chromatography (ethyl acetate/methanol) was performed to yield 18 g of 2-amino-4-anilino-6-methylaminopyrimidine. Synthesis was performed as in Synthetic example 1a-1 with 2-amino-4-anilino-6-methylaminopyrimidine, methyl m-methylbenzoate, and sodium methoxide. The product was purified by silica gel column chromatography using ethyl acetate/n-hexane and recrystallization from ethyl acetate/n-hexane to yield compound (6-14). (0405) The NMR spectrum of produced compound (6-14) is as follows. (0406) 1H-NMR (solvent: d6-DMSO, standard: tetramethylsilane) delta (ppm) 2.37 (3H, s) 2.75 (3H, d) 5.51 (1H, s) 6.87-6.91 (1H, m) 7.15-7.24 (2H, m) 7.34-7.38 (2H, m) 7.65-7.74 (4H, m) 8.95 (1H, s) 10.02 (1H, s) | |
In ethanol; water; at 80℃; for 1h; | (1) First 1.0g (6.097mmol) of Compound 1 (2-amino-4,6-dichloropyrimidine) and 10mL of ethanol into100mL round-bottomed flask was added 0.945g (12.194mmol) 40% (w / w) aqueous solution of methylamine, the reaction was refluxed for 1h. The reaction temperature was set to 80 deg. C. After completion of the reaction, the solvent was evaporated under reduced pressure, petroleum ether: ethyl acetate in a volume ratio = 3: 1 mixed solution as the eluant, by silica gel column chromatography to give a white solid, compound 2; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With sodium; at 180℃; for 12h; | 2-Amino-4-cyclohexylmethyloxy-6-methylaminopyririidine (NU6041) 2-Amino-4-chloro-6-methylaminopyrimidine (0.5 g, 2.25 mmol) was added to a stirred solution of sodium (0.062 g, 2.69 mmol) in cyclohexylmethanol (10 ml) under N2, and the reaction mixture was heated at 180 C. for 12 h. Solvents were removed in vacuo and the crude product was purified by chromatography on silica, employing dichloromethane:methanol (9:1) as eluent, to give the title compound as a white solid (0.03 g, 6%), m.p. 128-129 C.; numax/cm-1 3452 (NH), 2851 (NCH3), 1583 (NH2), 1514 (NH); deltaH (200 MHz, d6-DMSO) 1.04-1.31 (5H, m, C6H11), 2.78 (3H, d, NCH3, J=4.67 Hz), 4.02 (2H, d, OCH2), 5.10 (1H, s, C(5)H), 6.00 (2H, br s, NH2), 6.52 (1H, br d, NH, J=4.22 Hz); m/z (+EI) 236 (M+, 37%), 206 (MH+-NHMe, 31), 153 (M+-C6H11, 45), 140 (MH+-C6H11CH2O, 100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage 1 2-Amino-4-methylamino-6-chloropyrimidine STR28 10 g of 2-amino-4,6-dichloropyrimidine are suspended in 100 ml of ethanol. 11.80 g of methylamine are added as a 40% solution in water. The reaction mixture is refluxed for 3 hours. After it has returned to room temperature, 4 g of potassium hydroxide in solution in 40 ml of ethanol are added. After being stirred for half an hour the reaction mixture is filtered on paper. It is evaporated to dryness. The precipitate obtained is taken up in 25 ml of water, filtered off on sintered glass, rinsed with 25 ml of water and then dried in vacuum and over phosphorus pentoxide. 8.50 g of 2-amino-4-methylamino-6-chloropyrimidine are obtained. Yield=88% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3-chloro-benzenecarboperoxoic acid; In ethanol; | Stage 2 2-Amino-4-methylamino-6-chloropyrimidine 3-oxide STR29 4 g of <strong>[1005-37-4]2-amino-4-methylamino-6-chloropyrimidine</strong> are suspended in 50 ml of ethanol. After having cooled to 10 C., 11.9 g of meta-chloroperbenzoic acid are added dropwise as a solution in 100 ml of ethanol. At the end of addition, room temperature is regained and stirring is continued for 3 hours. The reaction mixture is cooled to 5 C. and then filtered on sintered glass. The precipitate obtained is recrystallized from 160 ml of a 2/3-1/3 ethanol-water mixture. 1.60 g of <strong>[1005-37-4]2-amino-4-methylamino-6-chloropyrimidine</strong> 3-oxide are obtained. Yield=36% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | To a mixture of beta-chloro-Lambda^-methyl^^-pyrimidinediamine (500 mg, 3.15 mmol), 2-acetyl- 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 ,2-dihydroindazolo[4,3- 6c][1 ,5]benzoxazepine (1.60 g, 4.10 mmol), tricyclohexylphosphine (22 mg, 0.08 mmol), and K2CO3 (1.31 g, 9.45 mmol) in 1 ,4-dioxane (4 mL) and water (6 mL) was added Pd2(dba)3 (27 mg, 0.03 mmol) under nitrogen, and the reaction mixture was heated for 40 minutes at 140 0C in a microwave reactor. The mixture was cooled to room temperature and filtered, and the resulting solid was washed with EtOAc and purified by reverse phase chromatography (gradient: 30% CH3CN/H2O to 40% CH3CN/H2O w/0.5% TFA) to afford a TFA salt of the title compound (169 mg, 16%) as a yellow solid. LC-MS (ES) m/z = 346 [M+H]+. 1H NMR (400 MHz, DMSOd6): delta 2.95 - 2.96 (d, J = 4.4 Hz, 3H), 6.46 (s, 1 H), 6.89 - 6.97 (m, 1 H), 7.03 (s, 1 H), 7.07 - 7.11 (m, 1 H), 7.26 - 7.30 (m, 2H), 7.47 (s, 1 H), 8.74 (bs, 1 H), 9.65 (s, 1 H), 12.14 (bs, 1 H), 12.68 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1-Synthesis of 1-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide To a suspension of 6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide (100 mg, 0.32 mmol) at 0 C. in DMF (3 mL) was added sodium hydride (19 mg of a 60% dispersion in mineral oil, 0.47 mmol). The reaction mixture was allowed to warm to RT over 15 minutes before the addition of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (75 mg, 0.47 mmol). The reaction mixture was then heated at 180 C. for 2 hr. The reaction mixture was allowed to cool to RT. The mixture was cooled to 0 C. and quenched by addition of water (1 mL) and the volatiles evaporated in vacuo. The mixture was diluted with sat ammonium chloride (20 mL) and extracted with ethyl acetate (3*50 mL). The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. Purification of the residue by column chromatography (Biotage, 55-100% ethyl acetate: heptanes) gave the title compound: 1H NMR (500 MHz, DMSO) delta 2.78 (3H, s), 3.08 (3H, s), 3.42 (3H, s), 6.24 (1H, s), 6.48 (2H, s), 7.08 (1H, s), 7.64 (1H, m), 7.79 (1H, m), 9.40 (1H, s); LC-MS: m/z=+438.0 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; | General procedure: General Procedure 5: To a mixture of a suitable chloropyrimidine derivative (1 equiv.) in DMF/water (9:1) is added the appropriate boronic acid (or boronic ester) derivative (1.1 equiv.), Na2003 (2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The mixture is heated at 120 00 overnight or in the microwave until the reaction iscomplete as shown by LCMS. The crude mixture is then purified by preparative HPLC to afford the desired product.Example 696-(4-tert-butylphenyl)-4-N-methylpyri midi ne-2,4-diam me.Prepared according to general procedure 5 from (4-tert-butylphenyl)boronic acidand <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong>. LCMS [M+H] 257; 1H NMR (400MHz, CD3OD) OH 7.77 (2H, d, J = 8.7 Hz), 7.53-7.48 (2H, m), 6.22 (1H, s), 2.93 (3H, s), 1.38 (9H, s). | |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 120℃; | General procedure: General Procedure 5: To a mixture of a suitable chloropyrimidine derivative (1 equiv.) in DMF/water (9: 1) is added the appropriate boronic acid (or boronic ester) derivative (1.1 equiv.), Na2C03 (2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The mixture is heated at 120 C overnight or in the microwave until the reaction is complete as shown by LCMS. The crude mixture is then purified by preparative HPLC to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; | General procedure: General Procedure 8: To a mixture of a suitable 4-chloropyrimidin-2-amine (1equiv.) in 1,4-dioxane/water (4:1) is added the desired boronic acid (or boronic ester) (1.3 equiv.), K2C03 (2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The mixture is heated at 95 C overnight or in a microwave until the reaction is complete asshown by LCMS. The crude mixture is purified by HPLC to afford the desiredproduct.Example 234-N-methyl-6-[1 -(4-methylbenzenesulfonyl)-1 H-indol-3-yl]pyrimidine-2,4-diamine.Prepared according to general procedure 8 from [1-(4-methylbenzenesulfonyl)-1 H-indol-3-yl]boronic acid and <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong>. LCMS[M+H] 394; 1H NMR (400 MHz, CD3OD) OH 8.36 (1H, s), 8.07 (1H, d, J = 8.3 Hz),7.93 (2H, d, J = 8.3 Hz), 7.83 (1 H, d, J = 7.9 Hz), 7.51 - 7.44 (1 H, m), 7.43 - 7.31(3H, m), 6.46 (1H, s), 3.04 (3H, s), 2.37 (3H, s). | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 95℃; | General procedure: General Procedure 8: To a mixture of a suitable 4-chloropyrimidin-2-amine (1 equiv.) in 1 ,4-dioxane/water (4: 1) is added the desired boronic acid (or boronic ester) (1.3 equiv.), K2C03 (2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The mixture is heated at 95 C overnight or in a microwave until the reaction is complete as shown by LCMS. The crude mixture is purified by HPLC to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 256 tert-butyl 4-{4-[2-am ino-6-(methylamino)pyrimidin-4-yl]-2-(methoxymethyl)phenoxymethyl}piperidine- 1 -carboxylate.mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), tert15 butyl 4-[4-(dimethoxyboranyl)-2-(methoxymethyl) phenoxymethyl]piperidine- 1-carboxylate (67 mg, 0.17 mmol), potassium carbonate (41 mg, 0.30 mmol) and palladium tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1,4- dioxane (5 mL) and water (1.5 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparativePLC. LCMS [M+H] 458. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 256 tert-butyl 4-{4-[2-amino-6-(methylamino)pyrimidin-4-yl]-2- (methoxymethyl)phenoxymethyl}piperidine-1-carboxylate. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), tert- butyl 4-[4-(dimethoxyboranyl)-2-(methoxymethyl)phenoxymethyl]piperidine-1- carboxylate (67 mg, 0.17 mmol), potassium carbonate (41 mg, 0.30 mmol) and palladium tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4- dioxane (5 mL) and water (1.5 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 458. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 2583-[2-am ino-6-(methylamino)pyrimidin-4-yl]-2-methylbenzonitrile.A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (3-cyano-2-methylphenyl)boronic acid (29 mg, 0.18 mmol), potassium carbonate (41mg, 0.30 mmol) and palladium tetrakis(triphenylphosphine)palladium (0) (9 mg,0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 900C overnight. The reaction mixture was concentrated and purified by preparative H PLC. LCMS [M+H] 240. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 258 3-[2-amino-6-(methylamino)pyrimidin-4-yl]-2-methylbenzonitrile. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (3- cyano-2-methylphenyl)boronic acid (29 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and palladium tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 240. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 2596-(4-methoxy-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine.A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (4- methoxy-2,3-dimethylphenyl)boronic acid (32 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9mg, 0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative H PLC. LCMS [M+H] 259. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 259 6-(4-methoxy-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (4- methoxy-2,3-dimethylphenyl)boronic acid (32 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 259. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 2606-(4-fluoro-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine.A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (4-fluoro-2,3-dimethylphenyl)boronic acid (30 mg, 0.18 mmol), potassium carbonate(41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at90C overnight. The reaction mixture was concentrated and purified bypreparative H PLC. LCMS [M+H] 247. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 260 6-(4-fluoro-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (4- fluoro-2,3-dimethylphenyl)boronic acid (30 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 247. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 2616-(2,3-dihydro-1-benzofuran-7-yl)-4-N-methylpyrimidine-2,4-diamine.A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (2,3-dihydro-1-benzofuran-7-yl)boronic acid (30 mg, 0.18 mmol), potassium carbonate(41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at90C overnight. The reaction mixture was concentrated and purified bypreparative HPLC. LCMS [M+H] 243. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 261 6-(2,3-dihydro-1-benzofuran-7-yl)-4-N-methylpyrimidine-2,4-diamine. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), (2,3- dihydro-1-benzofuran-7-yl)boronic acid (30 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 ml_) and water (1 ml_) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 243. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 2624-N-methyl-6-[2-methyl-5-(morpholine-4-sulfonyl) phenyl]pyrim idi ne-2,4-diam me.A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), [2-methyl-5-(morpholine-4-sulfonyl)phenyl]boronic acid (51 mg, 0.18 mmol),potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 9000 overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H] 364. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 262 4-N-methyl-6-[2-methyl-5-(morpholine-4-sulfonyl)phenyl]pyrimidine-2,4-diamine. A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (24 mg, 0.15 mmol), [2- methyl-5-(morpholine-4-sulfonyl)phenyl]boronic acid (51 mg, 0.18 mmol), potassium carbonate (41 mg, 0.30 mmol) and tetrakis(triphenylphosphine)- palladium (0) (9 mg, 0.008 mmol) in 1 ,4-dioxane (3 ml_) and water (1 ml_) was heated in a sealed tube at 90C overnight. The reaction mixture was concentrated and purified by preparative HPLC. LCMS [M+H]+ 364. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 3286-[3-(Aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine.Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirredmixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (2.00 mmol), [3-(aminomethyl)phenyl]boronic acid (1.3 eq.), sodium carbonate (3.2 eq.), dioxane(4 mL) and water (1 mL) in a tube. The tube was sealed and the reaction washeated at 9000 overnight. The solvent were removed in vacuum and to the remaining solid was added ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. The crude material was then purified by flash chromatography (0-*15 % MeOH/DCM) to give the title compound.LCMS [M+H] 230; 1H NMR (400 MHz, DMSO-d6) OH ppm 7.90 (1 H, 5), 7.75 (1 H, d, J=6.32 Hz), 7.35 - 7.42 (3 H, m), 6.82 (1 H, br. S), 6.21 (1 H, 5), 5.98 (2 H, 5), 3.79 (2 H, 5), 2.79 (3 H, d, J=4.80 Hz). | |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 328 6-[3-(Aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (2.00 mmol), [3- (aminomethyl)phenyl]boronic acid (1.3 equiv.), sodium carbonate (3.2 equiv.), dioxane (4 mL) and water (1 mL) in a tube. The tube was sealed and the reaction was heated at 90C overnight. The solvent were removed in vacuum and to the remaining solid was added ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. The crude material was then purified by flash chromatography (0?15 % MeOH/DCM) to give the title compound. LCMS [M+H]+ 230; 1 H NMR (400 MHz, DMSO-d6 delta ppm 7.90 (1 H, s), 7.75 (1 H, d, J=6.32 Hz), 7.35 - 7.42 (3 H, m), 6.82 (1 H, br. S), 6.21 (1 H, s), 5.98 (2 H, s), 3.79 (2 H, s), 2.79 (3 H, d, J=4.80 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 3296-[4-(Aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine.Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirredmixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (1.00 mmol), [4-(aminomethyl)phenyl]boronic acid (1.3 eq.), sodium carbonate (4.2 eq.), dioxane(4 ml) and water (1 ml) in a tube. The tube was sealed and the reaction washeated at 90C overnight. The solvent were removed in vacuum and to theremaining solid was added ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. The crude material was then purified by flash chromatography (0-*15 % MeOH/DCM) to give the title compound. LCMS [M+H] 230; 1H NMR (400 MHz, DMSO-d6) OH ppm 7.86 (2 H, d, J=7.58Hz), 7.38 (2 H, d, J=8.59 Hz), 6.19 (1 H, 5), 5.96 (2 H, 5), 3.76 (2 H, 5), 2.79 (3 H, d, J=4.80 Hz). | |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Example 329 6-[4-(Aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (1.00 mmol), [4- (aminomethyl)phenyl]boronic acid (1.3 equiv.), sodium carbonate (4.2 equiv.), dioxane (4 ml) and water (1 ml) in a tube. The tube was sealed and the reaction was heated at 90C overnight. The solvent were removed in vacuum and to the remaining solid was added ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. The crude material was then purified by flash chromatography (0?15 % MeOH/DCM) to give the title compound. LCMS [M+H]+ 230; 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.86 (2 H, d, J=7.58 Hz), 7.38 (2 H, d, J=8.59 Hz), 6.19 (1 H, s), 5.96 (2 H, s), 3.76 (2 H, s), 2.79 (3 H, d, J=4.80 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 5h; | Intermediate 41 -(3-aminophenyl)-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (1.00 mmol), (3- aminophenyl)boronic acid (1.3 equiv.), sodium carbonate (3.2 equiv.), 1 ,4- dioxane (4 mL) and water (1 mL) in a tube. The tube was sealed and the reaction was heated at 90C for 5 h and then concentrated. The crude material was taken up in ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate, concentrated and purified by flash chromatography (0?15 % MeOH in DCM) to give the title compound. LCMS [M+H]+ 216. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Sealed tube; | Intermediate 43 -(5-amino-2-methylphenyl)-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (3.0 mmol), (5-amino-2- methylphenyl)boronic acid (1.3 equiv.), sodium carbonate (3.2 equiv.), 1 ,4- dioxane (4 mL) and water (1 mL) in a tube. The tube was sealed and the reaction was heated at 90C for 5 h. The mixture was concentrated and purified by column chromatography (13 % MeOH in DCM) to give the title compound. LCMS [M+H]+ 230. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Sealed tube; | Intermediate 42 -(3-amino-2-methylphenyl)-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (3.00 mmol), (3-amino-2- methylphenyl)boronic acid (1.3 equiv.), sodium carbonate (3.2 equiv.), 1 ,4- dioxane (4 mL) and water (1 mL). The tube was sealed and the reaction was heated at 90C for 5 h. The mixture was concentrated and purified by column chromatography (13% MeOH in DCM) to give the title compound. LCMS [M+H]+ 230; 1 H NMR (400 MHz, DMSO-d6) delta ppm 6.88 (1 H, t, J=7.71 Hz), 6.71 - 6.81 (1 H, m), 6.61 (1 H, dd, J=7.96, 1.14 Hz), 6.44 (1 H, dd, J=7.58, 1.01 Hz), 5.90 (2 H, br. s.), 5.64 (1 H, s), 4.83 (2 H, s), 2.75 (3 H, d, J=4.55 Hz), 1.98 (3 H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Sealed tube; | Intermediate 44 6-(4-aminophenyl)-4-N-methylpyrimidine-2,4-diamine. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (1.0 mmol), 4-(tetramethyl- 1 ,3,2-dioxaborolan-2-yl)aniline (1.3 equiv.), sodium carbonate (3.2 equiv.), 1 ,4- dioxane (4 ml_) and water (1 ml_) in a tube. The tube was sealed and the reaction was heated at 90C for 5 h and then concentrated. The crude material was taken up in ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate, concentrated and purified by flash chromatography (0?15 % MeOH/DCM) to give the title compound. LCMS [M+H]+ 216; 1 H NMR (400 MHz, CDCIs) delta ppm 7.64 (2 H, d, J=8.53 Hz), 6.50 - 6.62 (3 H, m), 6.03 (1 H, s), 5.74 (2 H, s), 5.37 (2 H, s), 2.76 (3 H, d, J=4.77 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 15h;Sealed tube; | Step 1 : A mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (48 mg, 0.30 mmol), 3-(dihydroxyboranyl)benzoic acid (60 mg, 0.36 mmol), K2C03 (104 mg, 0.75 mmol) and palladium tetrakis(triphenylphosphine)palladium (0) (17 mg, 0.015 mmol) in 1 ,4-dioxane (3 mL) and water (1 mL) was heated in a sealed tube at 90C for 15 h. Concentrated and purified by preparative HPLC. LCMS [M+H]+ 245. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Sealed tube; | Example 327 1-{4-[2-Amino-6-(methylamino)pyrimidin-4-yl]phenyl}-2,2,2-trifluoroethan-1-one. Tetrakis(triphenylphosphine)palladium (0) (5 mol%) was added to a stirred mixture of <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (0.25 mmol), [4- (trifluoroacetyl)phenyl]boronic ester (1.3 equiv.), sodium carbonate (3.2 equiv.), dioxane (2 mL) and water (0.5 mL) in a tube. The tube was sealed and the reaction was heated at 90C for 5 hours. The mixture was then filtrated and purified by preparative HPLC. LCMS [M+H]+ 297. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With hydrogen iodide; sodium iodide; In acetone; at 60℃; for 12h; | Intermediate 17 ethylpyrimidine-2,4-diamine. To a suspension of 6-Chloro-4-N-methylpyrimidine-2,4-diamine (1.5 g, 9.43 mmol, 1 equiv.) in acetone (6.2 mL) was added sodium iodide (7.9 g, 52.8 mmol, 5.6 equiv.) and hydrogen iodide (15 mL). The reaction mixture was stirred at 60 C for 12 h. The solid was filtered off, dissolved in EtOAc, washed with NaHC03, brine, dried over MgS04 and concentrated under reduced pressure to afford the desired compound as an orange solid (1.7 g, 73 %). LCMS [M+H]+ 251 ; 1 H NMR (400 MHz, CDCI3) 56.27 (1 H, s), 2.80 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; at 80 - 100℃; | General procedure: General procedure 17: A mixture of the corresponding 6-chloro-4-N-(alkyl)- pyrimidine-2,4-diamine compound (1.0 equiv.), the appropriate arylboronic ester (1.5 equiv.), Pd(OAc)2 (0.10 equiv.), SPhos (0.20 equiv), and K3P03 (3.0 equiv.) was stirred in a suitable solvent (ethanol or a 5:2 mixture of 1-butanol and water) at 80 - 100 C until LCMS indicated full conversion. The crude mixture was then diluted with NaHC03 (aq) and extracted with DCM *3. The crude material was purified by preparative LC or by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; acetonitrile; at 120℃; for 0.166667h;Microwave irradiation; | Example 508 {2-[2-amino-6-(methylamino)pyrimidin-4-yl]phenyl}methanol <strong>[1005-37-4]6-chloro-4-N-methylpyrimidine-2,4-diamine</strong> (20 mg, 0,13 mmol), 1 ,3-dihydro-2, 1- benzoxaborol-1-ol (25 mg, 0, 19 mmol), K2C03 (78 mg, 0,57 mmol), Tetrakis(triphenylphosphine)palladium(0) (7,3 mg, 0,0060 mmol), MeCN (1 ,5 mL) and water (0,5 mL) were heated in the micro for 10 min at 120C. The organic phase was filtered and purified by basic prep-HPLC to afford {2-[2-amino-6- (methylamino)pyrimidin-4-yl]phenyl}methanol. LCMS [M+H]+ 231 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18 g | With hydrogenchloride; In 2-methoxy-ethanol; at 120℃; for 3h; | 2-Amino-4-anilino-6-methylaminopyrimidine was synthesized, via <strong>[1005-37-4]2-amino-4-chloro-6-methylaminopyrimidine</strong>, with 2-amino-4,6-dichloropyrimidine as a starting material. 2-Amino-4,6-dichloropyrimidine (32.8 g), a 40% aqueous methylamine solution (34.5 mL), and ethanol (300 mL) were mixed, followed by stirring at an internal temperature of 70 C. for 4 hours. Subsequently, the solvent was concentrated under reduced pressure, and crystallization from acetonitrile was performed. The product was collected by filtration and was used without purification for the subsequent step. The crude product of <strong>[1005-37-4]2-amino-4-chloro-6-methylaminopyrimidine</strong>, aniline (27.4 mL), methoxyethanol (100 mL), and hydrochloric acid (0.2 mL) were mixed, followed by stirring with heating at 120 C. for 3 hours. After cooling, the reaction solution was added to sodium bicarbonate water (500 mL)/ethyl acetate under ice cooling to extract the product with ethyl acetate. After concentration, purification by column chromatography (ethyl acetate/methanol) was performed to yield 18 g of 2-amino-4-anilino-6-methylaminopyrimidine. Synthesis was performed as in Synthetic example 1a-1 with 2-amino-4-anilino-6-methylaminopyrimidine, methyl m-methylbenzoate, and sodium methoxide. The product was purified by silica gel column chromatography using ethyl acetate/n-hexane and recrystallization from ethyl acetate/n-hexane to yield compound (6-14). (0405) The NMR spectrum of produced compound (6-14) is as follows. (0406) 1H-NMR (solvent: d6-DMSO, standard: tetramethylsilane) delta (ppm) 2.37 (3H, s) 2.75 (3H, d) 5.51 (1H, s) 6.87-6.91 (1H, m) 7.15-7.24 (2H, m) 7.34-7.38 (2H, m) 7.65-7.74 (4H, m) 8.95 (1H, s) 10.02 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(2) Sequentially added 1.0g (6.329mmol) Compound 2, 1.44g (7.5948mmol) Compound 3 (2,3-dichlorophenyl boronic acid), 30mL of ethylene glycol dimethyl ether (DME), 10mL of water, 3.35g (31.645mmol) of sodium carbonate put into 250mL round bottom flask, argon protection and stirred for 30 minutes. Followed by addition of 0.36g tetrakistriphenylphosphine palladium immediately, argon protection reflux for 48 hours. The reaction temperature was set to 90 deg. C. After completion of the reaction, the solvent was removed under reduced pressure, petroleum ether: ethyl acetate = volume ratio of 3: 1 mixed solution as the eluant, purification by silica gel column chromatography to give a white solid powder 4, MTH1 inhibitor TH287. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37 mg | With N-ethyl-N,N-diisopropylamine; In ethanol; at 150℃; for 2h;Sealed tube; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (200 mg; 1 ,3 mmol) was dissolved in Ethanol (10 ml) and N-Ethyldiisopropylamine (0,3 ml) was added. To this solution (R)-1-Pyrrolidin-3-yl-methanol hydrochloride (200 mg; (0610) 1,5 mmol) was given and the mixture was kept for 2h at 150C in the microwave. For work up the mixture was evaporated to dryness and purified by chromatography to give [(R)-1-(2-Amino-6-methylamino-pyrimidin-4-yl)- pyrrolidin-3-yl]-methanol (37mg) as beige crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.5 mg | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 150℃; for 2h;Sealed tube; | 6-Chloro-N -methyl-pyrimidine-2,4-diamine (20,00 mg; 0,13 mmol) is dissolved in dimethyl sulfoxide (5,00 ml) and N-ethyldiisopropylamine (70,00 muIota). 8-Oxa-3-aza-bicyclo[3.2.1]octane (21 ,00 mg; 0,14 mmol) is added and the mixture is heated for 2h at 150C in a closed vial. For work up the mixture is lyophilized and pyrified by HPLC giving 3,5 mg of the product as yellowish foam. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 180℃; for 72h; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (200 mg; 1 ,3 mmol) was dissolved in 1-Butanol (5 ml) and N-Ethyldiisopropyl amine (0,85 ml) was added. After the addition of 2-(4-Methoxy-benzyl)-piperidine hydrochloride (300 mg; 1 ,2 mmol) the mixture was stirred 72h at 180C. For work up the reaction mixture was evaporated to dryness and purified by prap-HPLC giving 30 mg of the desired product as beige solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 180℃; for 72h;Sealed tube; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (200 mg; 1 ,3 mmol) was dissolved in 1-Butanol (5 ml) and N-Ethyl diisopropyl amine (0,6 ml). 2-(2- Methoxy-benzyl)-piperidine (310 mg 1 ,5 mmol) was added and the mixture was stirred for 72h at 180C in a closed vessel. The reaction was evaporated and the residue purified by HPLC giving 56 mg of the product as beige crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16 mg | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 120℃; for 4h;Inert atmosphere; Sealed tube; | 6-Chloro-N4-methyl-2,4-pyrimidinediamine (150 mg; 0,9 mmol) was dissolved in 1 ,4-Dioxane (5 ml) and under nitrogen was added 3-phenyl- pyrrolidin-2-one (168 mg; 1 mmol), 4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene (55 mg; 0,1 mmol), potassium (III) phosphate (402 mg; 1,9 mmol) and Tris-(dibenzylidenaceton)-dipalladium (0) (87 mg; 0,1 mmol). The reaction was stirred for 4 firs at 120C in the microwave. The reactions were filtrated and evaporated to dryness. The residue was purified by prep. HPLC giving 16 mg of the desired product as light brown solid. (0634) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tert-butyl alcohol; at 160℃; for 48h; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (500 mg; 3 mmol) was dissolved in tert. butyl alcohol (15 ml) and 1 ,8-Diazabicyclo[5.4.0]undec-7-ene (1 ml) was added. After the addition of Azetidine-3-carboxylic acid (400 mg) the mixture was stirred at 160C for 48h. Then the mixture was evaporated in vacuum and the residue (1 g, brown oil) was used in the next step without further purification (0636) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 160℃; for 144h; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (50 mg; 0,3 mmol) was dissolved in 1-Butanol (4 ml) and N-Ethyldiisopropylamine (0,13 ml). 2-(1-Methyl-1- phenyl-ethyl)-pyrrolidine (65 mg; 0,35 mmol) was added and the reaction was stirred at 160C for 6 days turning into a yellow solution. The reaction mixture was evaporated under vacuo. The residue was extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered and evaporated under vacuum. The residue was purified by chromatography. All fractions with product mass were combined and basified with 1 N NaOH. The resulting precipitate was filtered by suction giving 14 mg of the product as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 150℃; for 72h; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (50 mg; 0,3 mmol) was dissolved in 1-Butanol (4 ml) and N-Ethyldiisopropylamine (0,13 ml). To this solution 2- (o-tolylmethyl)pyrrolidine (61 mg; 0,3 mmol) was added and the reaction was stirred at 150C for 3 days turning into yellow. The reaction mixture was evaporated to dryness under vacuum and the residue was extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered and evaporated under vacuum. The residue was purified by chromatography. All fractions with product mass were combined, basified with 1 N NaOH and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered and evaporated under vacuum giving 44 mg of the product as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 160℃; | -Chloro-N4-methyl-pyrimidine-2,4-diamine (50 mg; 0,3 mmol) was dissolved in 1-Butanol extra pure NF (4 ml) and N-Ethyldiisopropylamine for synthesis (0,13 ml) was added followed by 2-[(2-methoxyphenyl)methyl]pyrrolidine (66 mg; 0,33 mmol). The reaction was stirred at 160C over night during which the color changed into a yellow solution. (0644) The mixture was evaporated under vacuum. The residue was extracted with ethyl acetate/water. The organic layer was dried over sodium sulphate, filtered and evaporated under vacuum. The residue was suspended in diethylether and filtered by suction giving 55 mg of the product as brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
105 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 150℃; for 16h;Sealed tube; | To a solution of 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (80 mg; 0,5 mmol) in 1-Butanol (3 ml) in a microwave vial was added 2-(2- chlorobenzyl)pyrrolidine hydrochloride (152 mg; 0,7 mmol) and N- Ethyldiisopropylamine (0,3 ml). The reaction was stirred for 16 hrs at 150C and evaporated in vacuum for work-up. The residue was purified by HPLC giving 105 mg of the product as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8 mg | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 180℃; for 72h; | 6-Chloro-N4-methyl-pyrimidine-2,4-diamine (200 mg; 1 ,3 mmol) was dissolved in 1-Butanol (5 ml) and N-Ethyldiisopropylamine (0,6 ml) was added together with 2-(2-Chloro-benzyl)-piperidine (250 mg; 1 ,2 mmol). The reaction was stirred for 72h at 180C. For work-up the reaction was evaporated in vacuum and purified by HPLC giving 8 mg of the product as beige solid. |
Tags: 1005-37-4 synthesis path| 1005-37-4 SDS| 1005-37-4 COA| 1005-37-4 purity| 1005-37-4 application| 1005-37-4 NMR| 1005-37-4 COA| 1005-37-4 structure
[ 1007-11-0 ]
6-Chloro-N4,N4-dimethylpyrimidine-2,4-diamine
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6-Chloro-N-methylpyrimidin-4-amine
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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