Structure of 774-07-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 774-07-2 |
Formula : | C7H9N3O2S |
M.W : | 199.23 |
SMILES Code : | O=C(C1=C(N)NC(N=C1)=S)OCC |
MDL No. : | MFCD00614345 |
InChI Key : | DKTWKRWWQKVQQB-UHFFFAOYSA-N |
Pubchem ID : | 759149 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-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 |
---|---|---|
97% | In DMF (N,N-dimethyl-formamide); at 20 - 50℃; for 0.333333h; | Iodomethane (2.6 g, 18 mmol) was added to the hot solution (50 C.) of ethyl 4-amino-2-mercaptopyrimidine-5-carboxylate (3.0 g, 15 mmol) in N,N-dimethylformamide (150 mL) and stirred at room temperature for 20 min. Solvent was removed in vacuo and the solid residue was washed by water. After dried in vacuo, desired product was obtained as a white solid (3.1 g, 97%). [0304] HPLC (4 minute gradient) tR=2.14 min; MS m/z 214.1 (M+H)+ |
45.2 g (86%) | With potassium carbonate; In water; acetone; | a) A mixture of 49 g (246 mmol) of 4-amino-5-carbethoxypyrimidine-2-thiol and 42 g (304 mmol) of potassium carbonate in 400 ml of acetone was treated with 50 g (352 mmol) of iodomethane. After stirring for 3 hours 500 ml of water were added. The phases were separated and the aqueous phase was extracted twice with 300 ml of dichloromethane each time. The combined organic phases were washed with 100 ml of brine, dried over magnesium sulfate, filtered and evaporated to give 45.2 g (86%) of ethyl 4-amino-2-methylthiopyrimidine-5-carboxylate as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium carbonate; In ethanol; for 2h;Heating / reflux; | b) A stirred suspension of 473 g (2.377 mol) of <strong>[774-07-2]4-amino-5-carbethoxy-pyrimidine-2-thiol</strong> in 3.5 L of ethanol was treated with 180.4 g (1.307 mol) of potassium carbonate and 447.1 g (2.615 mol) of benzyl bromide. The mixture was heated at reflux for 2 hours then allowed to cool to room temperature overnight. The suspension was filtered and the solid washed with two 500 mL portions of ethanol, 2 L of water and two 500 mL portions of water. The product was dried in vacuo over phosphorus pentoxide at 50 C. to give 416 g (61%) of ethyl 4-amino-2-benzylthiopyrimidine-5-carboxylate as a cream solid of melting point 117-118 C. |
416 g (61%) | With potassium carbonate; In phosphorus pentaoxide; ethanol; water; | 34.2 Preparation of 4-Amino-2-benzylthiopyrimidine-5-carboxylate A stirred suspension of <strong>[774-07-2]4-amino-5-carbethoxy-pyrimidine-2-thiol</strong> (473 g, 2.377 mol) in 3.5 L of ethanol was treated with potassium carbonate (180.4 g, 1.307 mol) and benzyl bromide (447.1 g, 2.615 mol). The mixture was heated at reflux for 2 hours then allowed to cool to room temperature overnight. The suspension was filtered and the solid washed with two 500 mL portions of ethanol, 2 L of water and two 500 mL portions of water. The product was dried in vacuo over phosphorus pentoxide at 50 C. to give 416 g (61%) of ethyl 4-amino-2-benzylthiopyrimidine-5-carboxylate as a cream solid of melting point 117-118 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Example 5 [00154] This example illustrates the preparation of 4-amino-2-benzylthiopyrimidine-5-carboxaldehyde.; a) 272 g (4.0 mol) of sodium ethoxide (Lancaster) was stirred in 1 L of ethanol and treated with 304 g (4.0 mol) thiourea (Avocado). 676 g (4.0 mol) of ethyl ethoxymethylene cyanoacetate (Avocado) was added and the mixture heated at reflux for 8 hours. After cooling to room temperature overnight, the reaction mixture was treated sequentially with 2 L of water and 400 mL of acetic acid. The reaction mixture was heated at reflux for 30 minutes, cooled to room temperature, and the suspension filtered. The solid was washed three 500 mL portions of water, two 500 mL portions of acetone, and 500 mL of diethyl ether. The product was dried to give 473.3 g (60%) of 4-amino-5-carbethoxy-pyrimidine-2-thiol as a cream solid of melting point >250 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
473.3 g (60%) | With sodium ethanolate; acetic acid; thiourea; In diethyl ether; ethanol; water; | Example 34 4-Amino-2-benzylthiopyrimidine-5-carboxaldehyde Sodium ethoxide (272 g, 4.0 mol) (Lancaster) was stirred in 1 L of ethanol and treated with thiourea (304 g, 4.0 mol) (Avocado). Ethyl ethoxymethylene cyanoacetate (676 g, 4.0 mol) (Avocado) was added and the mixture heated at reflux for 8 hours. After cooling to room temperature overnight, the reaction mixture was treated sequentially with 2 L of water and 400 mL of acetic acid. The reaction mixture was heated at reflux for 30 minutes, cooled to room temperature, and the suspension filtered. The solid was washed three 500 mL portions of water, two 500 mL portions of acetone, and 500 mL of diethyl ether. The product was dried to give 473.3 g (60%) of 4-amino-5-carbethoxy-pyrimidine-2-thiol as a cream solid of melting point >250 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In dimethyl sulfoxide; at 20℃; for 0.5h; | A. Potassium-4-amino-2-tritylsulfanylpyrimidine-5-carboxylate Solid portions of Na2CO3 (3.7 g, 25 mmol) followed by triphenylmethylchloride (6.4 g, 23 mmol) were added, at ambient temperature, to a stirred solution of ethyl-4-amino-2-mercapto-pyrimidine-5-carboxylate (Lancaster; 5.0 g, 25 mmol) in DMSO (100 mL). After 30 min, the resulting suspension was diluted with H2O (500 mL) and extracted with dichloromethane (5*100 mL). The combined organic extract was washed with H2O (2*100 mL), dried using Na2SO4 and diluted with THF (100 mL). Solid KOTMS (90% tech., 7.4 g, 60 mmol) was immediately added to this solution of crude trityl protected sulfide and the resulting yellow suspension was stirred at reflux (1 h). After allowing to cool to ambient temperature, the resulting voluminous white solids were collected by filtration, washed with dichloromethane and dried in vacuo to afford the titled compound (8.0 g, 18 mmol, 78% yield): 1H NMR (300 MHz, DMSO-d6) δ 7.95 (s, 1H), 7.29-7.13 (m, 18H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate; In ethanol;Heating / reflux; | Example 264-Amino-2-[(2-[l-(3,4-dichlorobenzyl)piperidin-4-yl]amino}-2- oxoethyl)thio]pyrimidine-5-carboxylic acida) Ethyl 4-Amino-2-[(2- { [1 -(3,4-dichlorobenzyl)piperidin-4-yl]amino} -2- oxoethyl)thio]pyrimidine-5-carboxylate2-Chloro-iV-[l-(3,4-dichlorobenzyl)piperidin-4-yl]acetamide (0.1 g), ethyl 4-amino-2- mercaptopyrimidine-5-carboxylate (0.06 g) and sodium acetate (0.05 g) in ethanol (10 mL) 0 were heated under reflux overnight. The solvent was evaporated and the residue was purified by flash chromatography to afford the subtitle compound as a colourless solid (0.16O g).MS 496/498 [M+H]+ (APCI+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.8% | at 90℃;Inert atmosphere; | A mixture of ethyl 4-amino-2-mercaptopyrimidine-5-carboxylate (30 g, 151 mmol) and morpholine (100 mL) was heated at 90 C. overnight under argon. The mixture was then cooled and concentrated under reduced pressure. The residue was taken up in dichloromethane (300 mL), washed successively with water (200 mL), brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give ethyl 4-amino-2-morpholinopyrimidine-5-carboxylate as a white solid. (Yield 30 g, 78.8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.6% | at 90℃; | A mixture of ethyl 4-amino-2-mercaptopyrimidine-5-carboxylate (6 g, 30.1 mmol) and 1-methyl piperazine (20 mL) was heated at 90 C. overnight. The mixture was concentrated under reduced pressure. The residue was taken up in dichloromethane (50 mL) and washed once with water (50 mL), once with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was triturated with hexanes-ethyl acetate (9:1) to give 4-amino-2-(4-methyl-piperazin-1-yl)-pyrimidine-5-carboxylic acid ethyl ester as a yellow solid. (Yield 6.2 g, 77.6%). |
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