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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 7461-50-9 |
Formula : | C4H4ClN3 |
M.W : | 129.55 |
SMILES Code : | C1=CN=C(Cl)N=C1N |
MDL No. : | MFCD00194051 |
InChI Key : | LPBDZVNGCNTELM-UHFFFAOYSA-N |
Pubchem ID : | 345752 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | 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 |
---|---|---|
67% | In N,N-dimethyl-formamide; | Pre Step A 2-(4-Methyl-1-piperazinyl)-4-pyrimidinamine A mixture of 2-chloro-4-pyrimidinamine (300 mg, 2.316 mmol) and 1-methylpiperazine (771 mul, 6.95 mmol) in N,N-dimethylformamide (DMF) (3 ml) was heated to 220 C. via a microwave reactor for 60 min. The reaction was purified by RP-HPLC to yield 2-(4-methyl-1-piperazinyl)-4-pyrimidinamine (300 mg, 1.552 mmol, 67% yield). MS (ES+) m/z 194.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h;Sealed tube; Microwave irradiation; | Into a 30 mL sealed tube was added a solution of 2-chloropyrimidin-4-amine (589 mg, 4.55 mmol) in N,N-dimethylformamide (10 mL), 8-oxa-3-azabicyclo[3.2.1]octane (745 mg, 6.58 mmol) and potassium carbonate (1.59 g, 11.5 mmol). The reaction mixture was irradiated with microwave radiation for 1 h at 120 C. The resulting solution was diluted with H20 (20 mL). The resulting solution was extracted with ethyl acetate (3x30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by silica gel chromatography with dichloromethane/methanol (100:9.8) to afford 2-[8-oxa-3-azabicyclo[3.2.1]octan-3-yl]pyrimidin-4-amine (400 mg, 43%) as a white solid. LCMS (ESI): RT (min) = 1.00, [M+H]+ = 207, method = J. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 18h; | 2-Chloropyrimidin-4-ylamine (3.5 g, 27.0 mmol), <strong>[4045-25-4]4-methoxypiperidine hydrochloride</strong> (4.09 g, 27.0 mmol) and Cs2C03 (26.4 g, 81.0 mmol) were suspended in DMF (60 mL) and heated at 120 C for 18 h. The reaction mixture was partitioned between water and EtOAc. The aqueous phase was washed with EtOAc (x 2) and the combined organic phases were washed with brine, dried (MgSO i), and concentrated in vacuo affording the title compound as a solid (2.5 g). The aqueous phase was concentrated in vacuo and the slurry was extracted with EtOAc. The volatiles were removed in vacuo and the resulting residue was purified by chromatography (Si-PCC, gradient 0- 100% EtOAc in cyclohexane) and then triturated with cyclohexane affording a second batch of the title compound (2.38 g, 87% combining the two batches). lH NMR (400 MHz, CDC13) delta: 7.94 (1H, d, J=5.60 Hz), 5.74 (1H, d, J=5.60 Hz), 4.53 (2H s), 4.33-4.24 (2H, m), 3.47-3.37 (4H, m), 3.33-3.24 (2H, m), 1.98-1.87 (2H, m), 1.60-1.47 (2H, m). |
87% | With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 18h; | 2-Chloropyrimidin-4-ylamine (3.5 g, 27.0 mmol), <strong>[4045-25-4]4-methoxypiperidine hydrochloride</strong> (4.09 g, 27.0 mmol) and cesium carbonate (26.4 g, 81.0 mmol) were suspended in NN-dimethylformamide (60 mL) and heated at 120 C for 18 h. The reaction mixture was cooled to room temperature and partitioned between water and EtOAc. The aqueous phase was washed with EtOAc (x 2) and the combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo affording the title compound as a solid (2.5 g). The aqueous phase was concentrated in vacuo and the slurry was extracted with EtOAc. The volatiles were removed in vacuo and the resulting residue was purified via flash chromatography on silica gel (solvent gradient: 0%-100% EtOAc in cyclohexane) and then triturated with cyclohexane affording a second batch of 2-(4-methoxypiperidin-l -yl)pyrimidin-4-amine (2.38 g, 87% combined yield). LCMS (ESI): [M+H]+ = 209.2; lH NMR (400 MHz, CDC13) delta: 7.94 (1H, d, J=5.60 Hz), 5.74 (1H, d, J=5.60 Hz), 4.53 (2H s), 4.33-4.24 (2H, m), 3.47-3.37 (4H, m), 3.33-3.24 (2H, m), 1.98-1.87 (2H, m), 1.60-1.47 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With triethylamine; In isopropyl alcohol; at 80℃; | Step 1: 1-(4-Aminopyrimidin-2-yl) <strong>[59378-87-9]pyrrolidine-3-carboxylic acid</strong> 102a A 100 mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with <strong>[59378-87-9]pyrrolidine-3-carboxylic acid</strong> (1.20 g, 10 mmol), 2-chloropyrimidin-4-amine (1.30 g, 10 mmol), isopropyl alcohol (IPA, 40 mL), and TEA (6 mL). The mixture was heated at 80 C. overnight (O/N). After this time the reaction was cooled to room temperature (r.t.). It was then filtered and the filter cake was washed with DCM to afford 102a (1.4 g, 67%) as a pale yellow solid. MS: [M+H]+ 209.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of a mixture of 2-chloropyrimidin-4-amine (5.0 g, 38.5 mmol) and <strong>[72605-86-8]methyl 2-chlorothiazole-5-carboxylate</strong> (6.85 g, 38.5 mmol, 1 equivalent (eq)) in dry N,N- dimethylformamide (75 ml) was cooled to 0 C and was treated portionwise over 5 min with sodium hydride (60% w/w in mineral oil, 3.1 g, 76.9 mmol, 2 eq). The reaction mixture was stirred at 0 C for 1 h and warmed to ambient temperature for a further 1 h. The mixture was treated with saturated ammonium chloride, followed by saturated aqueous Na2C03 solution to reach pH 9, and the resulting mixture was extracted with 1: 1 mixture of dichloromethane and ethyl acetate. The organic extracts were combined, dried using a hydrophobic frit, and evaporated under reduced pressure. The residue was purified by chromatography on silica to afford the title compound as an off-white solid. LCMS retention time (RT): 2.70 (Method A), Mass mlz: 270.99 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.7 g | In a reaction apparatus with a reflux condenser, 2,3-dimethyl-6-chloro-2H-carbazole 18gAnd 14.5 g of 2-chloro-4-amino-pyrimidine were added to 220 mL of N,N-dimethylformamide.In an ice salt bath at 0 C under nitrogen protection,50 mL of a tetrahydrofuran solution containing 12% of sodium hydride in a content of 60% was slowly added dropwise.After the addition was completed, the temperature was raised to room temperature, and the reaction was continued for 5 hours.Then use the existing strong alkaline environment of the reaction system,100 mL of tetrahydrofuran solution in which 14 g of methyl iodide was dissolved was added dropwise.The reaction was continued for 6 h at room temperature, and new substances appeared in the reaction system monitored by TLC.And the content of the new substance in the reaction system is determined by HPLC to occupy 90% to 95%,The reaction system was cooled to 10 C, and then dilute hydrochloric acid was slowly added dropwise.The pH of the reaction solution was adjusted to be neutral, and then tetrahydrofuran was removed by evaporation under vacuum.The reaction solution was allowed to stand for a while, and then 70 mL of a saturated ammonium chloride solution was added to the reaction solution.Then, 250 mL of chloroform was added to the reaction solution.After stirring for 10 min, the organic phase was separated and the organic phase was concentrated.The concentrate is recrystallized from acetone and cyclohexane to giveN-(2-chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine 20.7 g; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26.8% | With DABCO; In water; dimethyl sulfoxide; at 60.0℃; for 6.0h; | A solution of Example 143a (2.0 g, 15.5 mmol) in DMSO/H2O (20 mL/ 20 mL) were treated with NaCN (1.52 g, 31.0 mmol) and DABCO (1.74 g, 15.5 mmol). The mixture was stirred at 60oC for 6 h. After reaction completed, the solvent was extracted by DCM (50 mL) and concentrated to give crude product, which was purified directly by Prep-HPLC to give the desired product Example 143b (500 mg, 26.8% yield) as a white solid. LCMS [M+1] + = 121.0 |
Tags: 4-Amino-2-chloropyrimidine | Pyrimidines | Chlorides | Amines | Organic Building Blocks | Heterocyclic Building Blocks | 7461-50-9
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