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| CAS No. : | 7749-47-5 | 
| Formula : | C6H9N3O | 
| M.W : | 139.15 | 
| SMILES Code : | C1=C(N=C(N)N=C1C)OC | 
| MDL No. : | MFCD00059768 | 
| InChI Key : | SNWZXTZIZWBIDQ-UHFFFAOYSA-N | 
| Pubchem ID : | 587236 | 
| GHS Pictogram: |   | 
| Signal Word: | Warning | 
| Hazard Statements: | H315-H319-H335 | 
| Precautionary Statements: | P261-P305+P351+P338 | 
* 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 | 
|---|---|---|
| 20% | With pyridine; at 0 - 60℃; for 17.0h; | Step 1: Synthesis of N-{4-[(4-methoxy-6-methylpyrimidin-2-yl)sulfamoyl] phenyl}acetamide 19.1 [00351] 4-(Acetylamino)benzenesulfonyl chloride (2.00 g, 8.56 mmol) was added at 0C to a stirred solution of <strong>[7749-47-5]4-methoxy-6-methylpyrimidin-2-amine</strong> (1.19 g, 8.56 mmol) in pyridine (dry, 20ml). The reaction mixture was allowed to reach rt and stirred for 15h then heated to 60C for 2h. The solvent was removed in vacuo by azeotroping with toluene (2 x 25ml), followed by n- heptane (2 x 25ml) to afford a brown oil which was purified by flash column chromatography (MeOH/DCM 0/100 to 5/95) to obtain 0.60g (20%) of N-{4-[(4-methoxy-6-methylpyrimidin-2- yl)sulfamoyl]phenyl}acetamide 19.1 a colourless solid. | 
| With pyridine; at 60℃; for 12.0h; | Step 1 - N-[4-[(4-methoxy-6-methyl-pyrimidin-2-yl)sulfamoyl]phenyl]acetamide (0431) [00295] To a suspension of 4-methoxy-6-methyl-pyrimidin-2-amine (4.00 g, 28.8 mmol) in pyridine (40 mL) was added 4-acetamidobenzenesulfonyl chloride (7.05 g, 30.2 mmol, CAS121-60-8). The reaction mixture was stirred at 60 C for 12 hr. On completion, the reaction mixture was concentrated and the residue was diluted with water, the solid was filtered, washed with dichloromethane (30 mL), and dried under vacuum to give the title compound. LCMS: (ES- ) m/z (M-H)- = 335.1, tR = 1.011. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 8% | With hydrogenchloride; sodium nitrite; In water; at 0 - 20℃; for 1.5h; | To a solution 2-amino-4-methoxy-6-methylpyrimidine (5 g, 35.97 mmol) in aqueous concentrated HCl (50 ml) was added NaNO2 (2.97 g, 43.16 mmol) in water(5 ml) slowly drop by drop over a period 30 min at 0oC and then the reaction mixture was stirred at room temperature for 1 hour. Then, the reaction mixture was quenched with 10 N sodium hydroxide solution then insoluble material was, filtered and filtrate was partitioned between brine and AcOEt and the aqueous layer was extracted with AcOEt. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a brown oil. The crude compound which upon purification by flash chromatography using (silica-gel: 100-200 mesh, AcOEt -petroleum ether; 10:90→ 15:85) gave 600 mg (yield 8%) of a white solid corresponding to 2-chloro-4-methoxy-6- methylpyrimidine. | 
| With sodium nitrite; In hydrogenchloride; water; | EXAMPLE 6 2-Chloro-4-methyl-6-methoxypyrimidine A solution of 25.4 g of 2-amino-4-methyl-6-methoxypyrimidine in 150 ml concentrated hydrochloric acid was cooled to ca. 0 C. and treated with a solution of 25.3 g of sodium nitrite in 50 ml water, added over a period of 30-40 minutes. The thick orange reaction mixture was stirred at room temperature for 4-5 hours and then adjusted to pH 10 by addition of 12.5N sodium hydroxide solution. The precipitate was filtered and extracted thoroughly with approximately 600 ml of hot ether. The organic layer was dried over magnesium sulfate and concentrated in vacuo to give 7.2 g of 2-chloro-4-methyl-6-methoxypyrimidine as a white, crystalline solid, m.p. 36-38 C. NMR(CDCl3): δ 6.5 (1H, s, heterocyclic H); 4.0 (3H, s, --OCH3); 2.4 (3H, s, --CH3). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 96.4% | In chlorobenzene; | EXAMPLE 2 1-[(N-Methylsulfonyl-N-methylamino)sulfonyl]-3-(4-methoxy-6-methyl-2-pyrimidyl)urea 52.0 g of ethyl (N-methylsulfonyl-N-methylamino)sulfonylcarbamate are dissolved in 500 ml of chlorobenzene, 27.8 g of 2-amino-4-methoxy-6-methylpyrimidine are added at room temperature, and the mixture is heated at 50 C. for 5 hours. After cooling to 0 C., the precipitate is filtered off. After washing with 100 ml of chlorobenzene, 68.8 g of the desired product of a purity of 98.9% are obtained; this corresponds to a yield of 96.4% of theory. The melting point of the product is 118-120 C. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 3611-92-5 ]
                                                    
                                                    [ 3611-92-5 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 19 1-[(N-methylsulfonyl-N-methylamino)-sulfonyl]-3-(4-methoxy-6-methyl-2-pyrimidinyl)-urea 13.9 g (0.1 mol) of 2-amino-4-methoxy-6-methylpyrimidine are suspended in 150 ml of methylene dichloride, and 21.4 g (0.1 mol) of N-methylsulfonyl isocyanate in 50 ml of methylene dichloride are added at 0 C. in the course of one hour. Stirring is continued for 15 hours at room temperature and the product is then precipitated with n-hexane. 20.4 g (58% of theory) of 1-[(N-methylsulfonyl-N-methylamino)-sulfonyl]-3-(4-methoxy-6-methyl-2-pyrimidinyl)-urea of melting point 118-120 C. are obtained. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 8 N-[(4-Methyl-6-methoxypyrimidin-2-yl)aminocarbonyl]-2-[5-(methylthio)-1,3,4-oxadiazol-2-yl]benzenemethanesulfonamide To a suspension of 0.33 g of 2-amino-4-methyl-6-methoxypyrimidine in 10 ml of acetonitrile was added 1 g of crude sulfonyl isocyanate prepared in Example 7. The suspension was stirred at room temperature overnight, then filtered. The residue was washed with 25 ml of ethyl ether and suction dried to give 0.7 g of the subject compound; m.p. 194-196 C. NMR(CDCl3, DMSO): ppm δ2.3 (s, 3H, CH3) 2.8 (s, 3H, SCH3); 3.8 (s, 3H, OCH3); 5.6 (s, 2H, CH2); 6.3 (s, 1H, pyrimidin); 7.4-7.9 (m, 4H, arom.). IR (nujol): 1710 cm-1 (C=O). | 

 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 98-88-4 ]
                                                    
                                                    [ 98-88-4 ]
 [ 93744-71-9 ]
                                                    
                                                    [ 93744-71-9 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 3 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminothioxomethyl]benzamide To a hot solution of 14 g of ammonium thiocyanate in 300 ml of acetonitrile was added 24 ml of benzoyl chloride. The mixture was heated on the steam bath for 30 minutes and filtered. The filtrate was heated with 21 g of 4-methoxy-6-methylpyrimidine-2-amine for 30 minutes and cooled. The product was collected by filtration and washed with a little acetonitrile to provide 28 g of N-[[(4-methoxy-6-methylpyrimidin-2-yl)aminothiocarbonyl]amino]benzamide, m.p. 193-195. IR (Nujol) 3290, 1720 cm-1. | 

 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 1189-71-5 ]
                                                    
                                                    [ 1189-71-5 ]
 [ 37493-34-8 ]
                                                    
                                                    [ 37493-34-8 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In CH3 NO2; nitromethane; dichloromethane; acetone; | EXAMPLE 2 Preparation of Methyl 3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-1-methyl-1H-indole-2-carboxylate To a stirred suspension of 2.92 g (0.021 mole) of 2-amino-4-methoxy-6-methylpyrimidine in 75 ml dry CH3 NO2 at -10 was addded dropwise under nitrogen via syringe 2.0 ml (0.023 mole) of chlorosulfonyl isocyanate at such a rate as to maintain the temperature below 0. The resulting clear solution was stirred 0.5 hour at -5 to -10 and then contacted dropwise with a solution of 3.97 g (0.021 mole) of methyl 1-methyl-1H-indole-2-carboxylate dissolved in 25 ml of dry nitromethane. Upon completion of the addition, 2.95 g (0.022 mole) of aluminum (III) chloride was added in one portion. The reaction mixture was stirred at reflux for 3 hours, then cooled to room temperature and poured into 300 ml H2 O. Dichloromethane was added and the layers were separated. The aqueous solution was extracted with two additional portions of CH2 Cl2 and the combined organic solutions washed with H2 O, dried over MgSO4 and evaporated in vacuo. Chromatography on silica gel with 5% acetone in CH2 Cl2 afforded 1.63 g of the desired product as a white solid, m.p. 200-203 (d). The infrared spectrum of the product included absorptions at 3190 (NH), 1715 (C=O), 1703 (C=O), 1340 and 1150 (SO2) cm-1, 'H NMR (CDCl3 /DMSO-d6) δ2.45 (s, 3H, pyrimidine CH3), 3.95 (s, 3H, OCH3), 4.0 (s, 6H, OCH3 and N--CH3), 6.37 (s, 1H, pyrimidine CH), 7.23-7.56 (m, 3H, indole CH), 8.18-8.47 (m, 1H, indole CH), 9.50 (s, 1H, NH), 13.08 (br s, 1H, NH). Mass spectral analysis showed m/e 139, STR31 | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 106-54-7 ]
                                                    
                                                    [ 106-54-7 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With formaldehyd; acetic acid; In methanol; toluene; | EXAMPLE 1 Preparation of 2-[(4-chlorophenylthio)methylamino]-4-methoxy-6-methylpyrimidine (intermediate) STR25 A mixture of 13.99 g of 2-amino-4-methoxy-6-methylpyrimidine (0.1 mole), 14.8 g of 4-chlorothiophenol (0.1 mole), 9.4 g of aqueous 35% formaldehyde (0.11 mole) and 1 g of acetic acid are heated under reflux for 1 hour in 100 ml of methanol. The resultant solution is clarified by filtration, diluted with 150 ml of toluene and then the solvent is removed in a rotary evaporator. The residue crystallises after standing for some time. The melting point is 78-82 after recrystallisation from hexane. The yield is 24 g (81% of theory). | 
 [ 288-88-0 ]
                                                    
                                                    [ 288-88-0 ]
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With formaldehyd; acetic acid; In methanol; | EXAMPLE 5 Preparation of 4-methoxy-6-methyl-2-(1,2,4-triazol-1-ylmethylamino)pyrimidine STR32 With stirring, a mixture of 13.9 g (0.1 mole) of 2-amino-4-methoxy-6-methylpyrimidine, 7 g (0.1 mole) of 1,2,4,-triazole, 9.4 g (0.11 mole) of aqueous 35% formaldehyde and 1 g of acetic acid in 100 ml of methanol is refluxed for 11/2 hours. First a clear solution forms, from which the reaction product precipitates in crystalline form after a time. After the reaction mixture has cooled, the crystalline title compound is filtered with suction and dried. Yield: 14 g. Melting point: 191-193 C. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With hydrogenchloride; In tetrahydrofuran; | EXAMPLE 6 Methyl (4-methoxy-6-methylpyrimidin-2-yl)carbamate 2-Amino-4-methoxy-6-methylpyrimidine (50 g) was added portion wise to 50% sodium hydride (42.8 g) in 1 L dry THF. After stirring for 1/2 hour, dimethyl carbonate (58.5 g) was added dropwise with cooling. The mixture was stirred under nitrogen for ~16 hours at ambient temperature. Concentrated HCl (80 ml) was added slowly and using external cooling a pot temperature of ~25 C. was maintained. Saturated aqueous NaCl (80 ml) was then added. The solvents were decanted from the precipitated solids and dried over Na2 SO4. Filtering and evaporating the solvents afforded the crude material which was recrystallized from hexane. 54 g m.p. 89-92.5 C. The infrared spectrum showed characteristic absorption bonds at 3400 and 1760 cm-1. | 
 [ 75-44-5 ]
                                                    
                                                    [ 75-44-5 ]
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

 [ 41570-86-9 ]
                                                    
                                                    [ 41570-86-9 ]
 [ 111-36-4 ]
                                                    
                                                    [ 111-36-4 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 22% | In dichloromethane; | c. N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-acetoxy-3,5-dichlorobenzenesulfonamide A mixture of 6.0 gm (0.02 mole) 2-acetoxy-3,5-dichlorobenzenesulfonamide, 0.1 gm 1,4-diaza[2.2.2]bicyclooctane (DABCO), 2.8 ml (0.025 mole) n-butyl isocyanate and 50 ml dry xylenes was heated to reflux and maintained at that temperature for 1 hour. Phosgene (0.03 mole, 1.3 ml) was then added dropwise, so as to maintain the reaction temperature >130. The reaction mixture was boiled under reflux for 3 hours after addition of phosgene, then cooled and filtered. The solvent was removed in vacuo and the residue was dissolved in 20 ml of methylene chloride and added directly to a stirred solution of 2-amino-4-methoxy-6-methylpyrimidine in 10 ml methylene chloride. The reaction was protected from atmospheric moisture and stirred overnight. Filtration of the solution removed excess starting material and the solution was evaporated to a residue. The residue was washed with 1-butyl chloride and filtered, giving 1.4 g (0.003 mole, 22% yield) of the sulfonylurea product. The nuclear magnetic resonance of the product shows peaks as follows: (singlet, 2.0δ, 3H, singlet, 2.2δ, 3H; singlet, 3.9δ, 3H; singlet, 6.1δ, 1H; 7.5-8.2δ, multiplet, 2H; br singlet, 8.6δ, 1H), consistent with the desired product. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 6 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methylsulfonyl-3-thiophenesulfonamide The crude 2-methylsulfonyl-3-thiophenesulfonyl isocyanate described above was dissolved in 100 ml of methylene chloride and 10 ml of this solution (0.3 g of crude isocyanate) was added to 200 mg of 4-methoxy-6-methyl-2-pyrimidinamine in methylene chloride containing a few crystals of DABCO. After stirring 3 days at room temperature, the precipitate was filtered and washed with ether to afford 250 mg of product, m.p. 204.5-206 d. The IR spectrum showed a carbonyl absorption at 1680 cm-1 indicative of a sulfonylurea. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 77888-53-0 ]
                                                    
                                                    [ 77888-53-0 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 5 N,N-Diethyl-N'-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-1,2-benzenedisulfonamide A mixture of 0.8 g of 2-amino-4-methoxy-6-methylpyrimidine, 2.8 g of the crude sulfonyl isocyanate from Example 4 and a few crystals of DABCO in 25 ml of acetonitrile was stirred at room temperature for 16 hours. A small amount of unreacted aminopyrimidine was filtered off and the filtrate concentrated in-vacuo to give a hard glass. Crystallization from methanol gave 0.9 g of N,N-diethyl-N'[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-1,2-benzenedisulfonamide as a white solid, m.p. 170-2. Anal. Calcd. for C17 H23 N5 O6 S2: C, 44.62; H, 5.07; N, 15.31. Found: C, 44.5, 44.4; H, 5.09, 5.09; N, 15.4, 15.5. NMR(DMSO-d6)δ: 0.9-1.2 [t,6.0H, (CH3 CH2)2 N-]; 2.3 (S, 2.8H, Het--CH3); 3.1-3.5 [qt, 4.3H, (CH3 CH2)2 N-]; 3.9 (S, 3.0H, Het--OCH3); 6.5 (S, 0.9H, Het--H); 7.7-8.5 (m, 4.3H, 4 aromatics); 10.6 (S, 1.0H, NH); 13.4 (S, 0.8H, NH). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 79163-69-2 ]
                                                    
                                                    [ 79163-69-2 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 5 8-nitro-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-1-naphthalenesulfonamide To 0.55 g (0.004 mol) of 2-amino-4-methoxy-6-methylpyrimidine dissolved in 5 ml of dry methylene chloride in a magnetically stirred 50 ml round bottom flask equipped with reflux condenser protected from moisture was added 4 ml of a methylene chloride solution of 1.0 g (0.004 mol) of 8-nitro-1-naphthalenesulfonylisocyanate. The reaction mixture was stirred with heating under reflux for ~16 hours. The cooled reaction mixture was concentrated in vacuo. The crude product was isolated by elutriation with chlorobutane in the usual manner to yield an off white solid, m.p. 145-154. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 3 2-Hydroxy-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzenesulfonamide, methanesulfonate To a suspension of 0.6 g 2-amino-4-methoxy-6-methylpyrimidine in 10 ml dry methylene chloride is added 1.1 g 2-hydroxybenzenesulfonylisocyanate, methanesulfonate. The reaction exotherms mildly and is then stirred for 1/2 hour. The solvent is evaporated under reduced pressure. The resultant mixture is triturated with diethylether and filtered to give 0.95 g white solid m.p. 189-190 C. The infrared spectrum shows absorption bands at 1700, 1615, 1560, 1370 cm-1. Calc. for C-40.4, H-3.87, N-13.4. Found C-40.2, H-3.77, N-13.6. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 90139-98-3 ]
                                                    
                                                    [ 90139-98-3 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With hydrogenchloride; sodium hydroxide; In water; acetonitrile; | EXAMPLE 4 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-pyridinesulfonamide To a stirred suspension of 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 20 ml of dry acetonitrile at room temperature is added 2.2 g of 2-pyridinesulfonylisocyanate. The mixture is stirred for several hours and filtered. Evaporation of the filtrate yields a solid residue which is stirred in approximately 30 ml of water while adjusting the pH of this mixture to 11 by the addition of 10% NaOH. This solution is filtered, the filtrate pH adjusted to pH 7 by adding 10% hydrochloric acid and the resulting neutral solution again filtered. The desired product is then precipitated from this filtrate by adjusting the pH to 2, collecting in a sintered funnel and drying in a vacuum oven at room temperature. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With sodium hydroxide; In dichloromethane; water; | EXAMPLE 5 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide To a stirred suspension of 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 30 ml of anhydrous methylene chloride was added at ambient temperature 2.4 g of 2-methoxycarbonylbenzenesulfonylisocyanate. After stirring for 16 hours, the foregoing mixture was filtered to remove unreacted amine, and the filtrate evaporated at temperatures up to 40 and reduced pressure. The resultant residue was stirred in 25 ml of water, the pH adjusted to 10 by the addition of 50% sodium hydroxide and the solution filtered. Acidification of the filtrate to pH 3 with hydrochloric acid caused precipitation of the desired product which was removed by filtration and dried to yield 0.8 g of product melting at 173-179. It showed infrared absorption peaks at 1720, 1680, 1630 and 1550 cm-1, consistent for N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide. | |
| With sodium hydroxide; In dichloromethane; water; | EXAMPLE 5 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide To a stirred suspension of 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 30 ml of anhydrous methylene chloride was added at ambient temperature 2.4 g of 2-methoxycarbonylbenzenesulfonyl isocyanate. After stirring for 16 hours, the foregoing mixture was filtered to remove unreacted amine, and the filtrate evaporated at temperatures up to 40 and reduced pressure. The resultant residue was stirred in 25 ml of water, the pH adjusted to 10 by the addition of 50% sodium hydroxide and the solution filtered. Acidification of the filtrate to pH 3 with hydrochloric acid caused precipitation of the desired product which was removed by filtration and dried to yield 0.8 g of product melting at 173-179. It showed infrared absorption peaks at 1720, 1680, 1630 and 1550 cm-1, consistent for N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 8 N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzothiophene-3-sulfonamide To 25 ml of anhydrous acetonitrile containing 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine was added 2.4 g of benzothiophene-3-sulfonyl isocyanate with stirring. The mixture was heated to boiling, allowed to cool to room temperature and then stirred overnight. The resultant precipitate was filtered off and washed with ether to yield 2 g of the desired product, m.p. 180-181 C. It showed absorption by NMR (60 MC) at 2.24 δ (6-CH3 group), 3.8 δ (4-OCH3), 6.2 δ (5-H on pyrimidine), 7-8 δ (aryl H's on benzo) and 8.3 δ (H on thiophene portion). Anal. Calcd. for C15 H14 N4 O4 S2: C, 47.61; H, 3.77; N, 14.81. Found: C, 47.59; H, 3.88; N, 14.83. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 12 N-[(4-Methoxy-6-methyl-2-pyrimidinyl)aminocarbonyl]-4-nitrothiophene-2-sulfonamide To 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 25 ml of anhydrous acetonitrile was added 2.4 g of 4-nitrothiophene-2-sulfonyl isocyanate with stirring at ambient temperature. After stirring for sixteen hours, the mixture was filtered and the precipitate washed with 1-chlorobutane. It melted at 155 with decomposition and showed an infrared absorption spectrum with peaks at 1700, 1620 and 1570 cm-1 consistent for the desired structure. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With 1,4-diaza-bicyclo[2.2.2]octane; In dichloromethane; | EXAMPLE 10 2-(1-Cyclopentenyl)-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzenesulfonamide A mixture of 2-amino-4-methoxy-6-methylpyrimidine (0.45 g, 3.2 mmol), methylene chloride and DABCO (ca. 10 mg) was contacted with 2-(1-cyclopentenyl)benzenesulfonyl isocyanate in methylene chloride solution at ambient temperature. After approximately 20 minutes the product crystallized from the reaction mixture and was collected by filtration and rinsed with ether. In this manner, 0.35 g of product was obtained, m.p. 235-236. The infrared spectrum exhibited a carbonyl absorption at 1710 cm-1 indicating the title compound. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With hydrogenchloride; In tetrahydrofuran; | EXAMPLE 6 Methyl (4-methoxy-6-methylpyrimidin-2-yl)carbamate To a suspension of 50 g of 2-amino-4-methoxy-6-methylpyrimidine in 1000 ml of tetrahydrofuran was added portionwise, under a nitrogen atmosphere, 42.8 g of 50% sodium hydride while cooling the reaction flask in an ice-water bath. After stirring one hour at 25 C., 58.5 g of dimethylcarbonate was added dropwise at 5 to 25 C. The suspension was stirred about 16 hours at ambient temperature, then 80 ml of concentrated hydrochloric acid was added dropwise while maintaining a reaction temperature of 20 to 25 C. with external ice-bath cooling. The suspension was stirred 0.5 hour, filtered, and the filtrate was dried over sodium sulfate and then concentrated in vacuo. The residue was recrystallized from hexane to yield 54 g of the title compound, m.p. 89-92.5 C. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

 [ 87473-77-6 ]
                                                    
                                                    [ 87473-77-6 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 3 2,3-Dihydro-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-5-nitro-1H-indene-4-sulfonamide To 0.69 g of 2-amino-4-methoxy-6-methylpyrimidine suspended in 5 ml of anhydrous methylene chloride was added with stirring one fifth of the solution of 2,3-dihydro-5-nitro-1H-indenesulfonyl isocyanate prepared in Example 1. After stirring at reflux for 16 hours, the methylene chloride was removed in vacuo on a rotary evaporator and the residue was triturated with 1-chlorobutane and methylene chloride to yield a solid which decomposed at 75-93. This product showed absorption peaks by infrared spectroscopy at 3400 cm-1 (NH), 1670 cm-1 (CO), 1540 cm-1 (NO2) and 1360 cm-1 (SO2). The structure was confirmed by Proton Magnetic Resonance absorption peaks at 7.6 ppm (aromatic CH), 6.4 ppm (pyrimidine CH), 2.8-3.6 ppm (cyclic CH2) and 3.9 ppm (CH3 O). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 81403-60-3 ]
                                                    
                                                    [ 81403-60-3 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; toluene; | EXAMPLE 4 STR16 13.9 g of 2-amino-4-methoxy-6-methylpyrimidine were dissolved in 150 ml of dry dichloromethane. To this solution was added dropwise a solution of 28.5 g of 2-biphenylylsulfonyl isocyanate in 40 ml of toluene over an hour. During this addition, the internal temperature was maintained at room temperature. When the addition was finished, the mixture was stirred at room temperature for 10 hours to complete the reaction. After completion of the reaction, the mixture was concentrated to about half the volume by evaporating dichloromethane under reduced pressure. The resultant colorless crystals were filtered. The crystals were then washed with a small amount of ether and dried to obtain 34.6 g of N-2-biphenylylsulfonyl-N'-(4-methoxy-6-methylpyrimidin-2-yl)urea; m.p. 199-202 C. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In acetonitrile; | EXAMPLE 4 Methyl 3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiophenecarboxylate To 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 30 ml of anhydrous acetonitrile was added at ambient temperature, with stirring 3.6 g of 2-methoxycarbonyl-3-thiophenesulfonylisocyanate. The mixture was heated to the boiling point and then allowed to cool to ambient temperature. After stirring for sixteen hours the precipitate present in the mixture was filtered off and washed with anhydrous ethyl ether. The product thus obtained which melted at 165-173 showed absorption peaks by infrared spectroscopy at 1720 and 1700 cm-1, consistent for the carbonyl groups in the desired product. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 76627-33-3 ]
                                                    
                                                    [ 76627-33-3 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With hydrogenchloride; sodium hydroxide; In water; acetonitrile; | EXAMPLE 4 2-Chloro-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-3-pyridinesulfonamide To a stirred suspension of 1.4 g of 2-amino-4-methoxy-6-methylpyrimidine in 20 ml of dry acetonitrile at room temperature was added 2.2 g of 2-chloropyridine-3-sulfonylisocyanate. The mixture was stirred for several hours and filtered. Evaporation of the filtrate yielded a solid residue which was stirred in approximately 30 ml of water while adjusting the pH of this mixture to 11 by the addition of 10% of NaOH. This solution was filtered, the filtrate pH adjusted to pH 7 by adding 10% hydrochloric acid and the resulting neutral solution was again filtered. The desired product was then precipitated from this filtrate by adjusting the pH to 2, collected in a sintered funnel and dried in a vacuum oven at room temperature. It melted at 165-168. By using the procedure of Examples 2 and 3 with the appropriately substituted 2-aminopyrimidine and the appropriately substituted pyridine-3-sulfonamide, or the procedure of Example 4 with an equivalent amount of a 2-aminopyrimidine and appropriately substituted sulfonylisocyanate or isothiocyanate, the compounds of Table II can be prepared. | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 5 1,3-Dihydro-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzo[c]furan-4-sulfonamide A 7.0 ml portion of the methylene chloride solution of 1,3-dihydrobenzo[c]furan-4-sulfonyl isocyanate prepared in Example 4 was added to a stirred suspension of 0.78 g of <strong>[7749-47-5]4-methoxy-6-methylpyrimidin-2-amine</strong> in 20 ml of methylene chloride. After several minutes the amine dissolved, followed by formation of a precipitate. After stirring for 1.75 hours, the solid was collected, washed with methylene chloride and 1-chlorobutane, then dried to give 1.4 g of 1,3-dihydro-N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]benzo[c]furan-4-sulfonamide, m.p. 190-194 (d). IR(nujol null): C=O (1725 cm-1). NMR (CDCl3 /TFA)δ: 2.6 (s, 3H, CH3); 4.1 (s, 3H, OCH3); 5.15 (broad s, 2H, CH2); 5.45 (broad s, 2H, CH2); 6.6 (s, 1H, pyrimidine CH); 7.5-7.8 (m, 2H, aromatic); and 7.8-8.2 (m, 1H, aromatic). | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In hexane; dichloromethane; | EXAMPLE 1 N-[(4-Methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-chlorocyclohexylsulfonamide 41.7 g (0.3 mole) of 2-amino-4-methoxy-6-methylpyrimidine were suspended in 500 ml of dichloromethane and a solution of 71.5 g (0.32 mole) of 2-chlorocyclohexylsulfonyl isocyanate in 200 ml of dichloromethane was added dropwise at 0 C. The reaction mixture was stirred a further 18 hours at room temperature, cooled to 0 C. and n-hexane was added. The precipitated reaction product was filtered off with suction and washed with n-hexane. 84.9 g (78% of theory) of N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-chlorocyclohexylsulfonamide were obtained, having a melting point of 145-148. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 2 N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-chlorobenzenesulfonamide To a suspension of 280 g of 2-amino-4-methoxy-6-methylpyrimidine in 2000 ml of methylene chloride was added 434 g of 2-chlorobenzenesulfonyl isocyanate with stirring. The resultant mixture was stirred for 16 hours, cooled to 10 and filtered to yield 470 g of a solid melting at 195-196. Mass spectrographic analysis showed this product to have a molecular weight of 356. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In dichloromethane; | EXAMPLE 5 N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-furansulfonamide To a solution of 2.10 g of 2-furansulfonyl isocyanate in 40 ml of methylene chloride was added 1.60 g 2-amino-4-methoxy-6-methylpyrimidine. The resulting mixture was stirred for 1 hour at room temperature, then refluxed for 15 minutes, and the solvent was removed under vacuum. The solid obtained was allowed to stand under ethyl ether containing a trace of acetonitrile for one day, and was then filtered and dried to give the desired product melting at 185-188 (dec). By using an equivalent of an appropriate 2-aminopyrimidine and an appropriately substituted thiophene or furansulfonyl isocyanate, the following compounds of Table II can be prepared by the procedures of Examples 3-5: example 6 | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 50% | With iodine; In methanol; at 20℃; for 2.0h; | General procedure for thiocyanation of aminopyrimidine derivatives: Ammonium thiocyanate (3 mmol) and iodine (1.0 mmol) are added at room temperature to a stirred solution of the corresponding aminopyrimidine derivative (1.0 mmol) in methanol (10 mL). After completion of the reaction (TLC control), a sodium thiosulfate solution [20% (w/v)] is added to destroy the remaining iodine. The solid formed is filtered off, washed with water, and recrystallized from a methanol/water solution. For more details see Table 1 and Supplementary data. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 63% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 23℃; for 0.333333h; | Example 15: preparation of 2-(dimethylamino)-4-(10-hydroxydecyl)-6- methoxypyrimidin-5-ol (Compound D); 4-methoxy-N,N,6-trimethylpyrimidin-2-amine:; To a stirred solution containing 1.0 g (7.19 mmol) of <strong>[7749-47-5]4-methoxy-6-methylpyrimidin-2-amine</strong> in 10 mL of anf DMF were added 1.35 mL (21.6 mmol) of methyl iodide followed by 853 mg (21.6 mmol) of 60% suspension of sodium hydride in mineral oil. The reaction mixture was stirred at 23 C for 20 min. The reaction mixture was quenched with water and concentrated under diminished pressure in order to remove as much DMF as possible. The residue was dissolved in 70 mL of ethyl acetate and washed with 50-mL portions of water and brine respectively. The organic solution was dried (MgS04) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 x 5 cm). Elution with 4:1 hexanes-ethyl acetate afforded the expected product as colorless oil: yield 755 mg (63%); silica gel TLC Rf 0.25 (4: 1 hexanes-ethyl acetate ); 1H NMR(CDC13) δ 2.22 (s, 3H), 3.12 (s, 6H), 3.83 (s, 3H) and 5.76 (s, 1H); 13C-NMR (CDC13) δ 24.07, 36.76, 36.76, 52.68, 93.74, 162.24, 167.70 and 170.24; mass spectrum (APCI+), m/z 168.1135 (M+H) (C8Hi4N30 requires 168.1137). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]
 [ 38464-20-9 ]
                                                    
                                                    [ 38464-20-9 ]
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With hydrogenchloride; In tetrahydrofuran; 1,4-dioxane; dichloromethane; at 0 - 80℃; for 28.5h; | 1,2-bis(trimethylsilyl)oxy)cyclobut-1-ene (500 mg, 2.17 mmol) was added to a solution of -4-methoxy-6methylpyrimidine (241 mg, 1.736 mmol) in 1.0M HCl/Dioxane (2 ml), dichloromethane (8 ml), THF (8 ml) at 0 C. After 30 mins, the mixture was heated at 80 C. for 28 hrs monitored by TLC (10% methanol in chloroform Product Rf: -Starting: -0.4, Product: -0.35) Indicated formation of product. LCMS indicated formation of 10% product with desired mass peak. Solvent was removed under vacuum and residue was purified by column chromatography over silica gel (0-10% methanol in Dichloromethane) after 3 repeated chromatographic purifications, 9 mg crude compound was isolated, which was characterized by LCMS.Yield=9 mgAnalytical DataMol. wt 207.17In LCMS MH+ seen at 208 HPLC purity 73% | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With magnesium sulfate; In ethanol; at 80℃; | General procedure: A mixture of an aldehyde (1.0 eq), magnesium sulfate (100 mg) and an amine (1.0 eq) in ethanol was heated at 80 C overnight. The reaction mixture was filtered. The formation of the imine was quantitative and the filtrate containing the imine was used in the next step without purification. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 82% | for 6.0h;Reflux; | General procedure: In a 25 mL two neck round bottom flask, adapted with a reflux condenser, was placed 2-aminopyridine (0.94 g. 10 mmol) with an excess of N,N-dimethylformamide dimethyl acetal (9mL), and the mixture refluxed for 6 h, until the starting materials (TLC) disappeared. The excess of DMFDMA was removed by adding toluene to the reaction mixture, followed by solvent evaporation under reduced pressure. The compound was further purified by re-crystallization from ethyl alcohol. The amidine was isolated as a yellow semisolid. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 11% | With triethylamine; at 20℃; for 24.0h;Cooling with ice; | General procedure: To a solution of substituted heteroaromatic amine (1.00 mmol) in dichloromethane, DMF or THF (2 mL) triethylamine (1.10 mmol) was added. The mixture was cooled in an ice bath and acryloyl chloride (1.05 mmol) was added dropwise. The reaction mixture was stirred for 24 hours at room temperature and extracted with water (3 × 3 mL). Subsequently, the aqueous layer was extracted with ethyl ether (3 × 5 mL). The combined organic layers were dried over anhydrous MgSO4 and filtered. After evaporation of solvents, the residue was purified on a silica column with chloroform:methanol mixtures (100:1, 50:1 v/v) as eluents to afford the respective acrylamides 10. | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 37% | With copper(l) iodide; diiodomethane; iodine; isopentyl nitrite; In tetrahydrofuran; for 3.0h;Reflux; Inert atmosphere; | To a stirred solution containing 3.00 g (21.6 mmol) of 2-amino-4-methoxy-6-methylpyrimidine, 5.46 g (21.6 mmol) of iodine, 4.31 g (22.6 mmol) of CuI and 2.50 mL (30.9 mmol) of CH2I2 in 120 mL of anhydrous THF was added 10.5 mL (78.2 mmol) of isoamylnitrite. The reaction mixture was stirred at reflux for 3 h. The cooled reaction mixture was filtered through Celite and the Celite pad was washed with CH2Cl2. The combined organic phase was washed with water and then with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (20 * 5 cm). Elution with hexane followed by 95:5 hexane/Et2O and then 80:20 hexane/Et2O afforded 10 as a yellowish solid: yield 2.01 g (37%); mp 43-44 C; silica gel TLC Rf 0.35 (4:1 hexane/Et2O); 1H NMR (CDCl3) δ 2.37 (s, 3H), 3.93 (s, 3H) and 6.50 (s, 1H); 13C NMR (CDCl3) δ 23.7, 54.6, 106.5, 127.4, 169.0 and 169.1; mass spectrum (APCI), m/z 250.9675 (M+H)+ (C6H8N2OI requires m/z 250.9682). | 
| 37% | With copper(l) iodide; iodine; isopentyl nitrite; In tetrahydrofuran; dichloromethane; for 3.0h;Reflux; | To a stirred solution containing 3.00 g (21.6 mmol) of 2-amino-4-methoxy-6- methylpyrimidine, 5.46 g (21.6 mmol) of iodine, 4.31 g (22.6 mmol) of CuT and 2.5 mL (30.9 mmol) of CH212 in 120 mL of anhydrous THF was added 10.5 mL (78.2 mmol) of isoamylnitrite. The reaction mixture was stirred at reflux for 3 h. The reaction mixture was allowed to warm to room temperature and then filtered through Celite, and the Celite pad was washed with CH2C12. The combined organic phase was washed with water and then with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (20 x 5 cm). Elution with hexane followed by 95:5 hexane-Et20 and then 80:20 hexane-Et20 afforded 35 as a yellowish solid: yield 2.01 g (3 7%); mp 43-44 C; silica gel TLC Rf0.35 (4:1 hexane-Et20); ‘H NMR (CDC13, 400 MHz) ö 2.37 (s, 3H), 3.93 (s, 3H) and 6.50 (s, Ill); ‘3C NMR (CDCI3, 100 MHz) 23.7, 54.6, 106.5, 127.4, 169.0 and 169.1; mass spectrum (APCI), m/z 250.9675 (M+H) (C6H8N201 requires 250.9682). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In toluene; for 4.0h;Reflux; | The mixture of 9 (about 2.0 mmol from last step) and 2-amino-pyrimidine/triazine derivatives (2.0 mmol) in toluene was heated to reflux. Along with the azeotrope of ethanol and toluene was distilled out of the reaction system continuously, a small amount of fresh toluene was added if necessary. Heating was stopped until the complete consumption of 9 which was indicated by TLC (petroleum ether : ethyl acetate = 1 : 1). After the reaction mixture was cooled to room temperature and allowed to stand for a few hours, the forming precipitate was collected by suction filtration and washed with small amounts of toluene and ethyl acetate to afford desired compounds 10a-q. They could be further purified on silica gel column chromatography (eluted by 20-40 acetone in petroleum ether). | 
 [ 7749-47-5 ]
                                                    
                                                    [ 7749-47-5 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In toluene; for 4.0h;Reflux; | The mixture of 9 (about 2.0 mmol from last step) and 2-amino-pyrimidine/triazine derivatives (2.0 mmol) in toluene was heated to reflux. Along with the azeotrope of ethanol and toluene was distilled out of the reaction system continuously, a small amount of fresh toluene was added if necessary. Heating was stopped until the complete consumption of 9 which was indicated by TLC (petroleum ether : ethyl acetate = 1 : 1). After the reaction mixture was cooled to room temperature and allowed to stand for a few hours, the forming precipitate was collected by suction filtration and washed with small amounts of toluene and ethyl acetate to afford desired compounds 10a-q. They could be further purified on silica gel column chromatography (eluted by 20-40 acetone in petroleum ether). | 

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