2-(4-Morpholino)-4,6-disubstituted pyrimidine/s-triazine compounds, salts thereof, and application of compounds or salts

[0033] The 2-(4-morpholinyl)-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl)amino)-6-(pyridinyl or pyrimidinyl)pyrimidine or The synthesis method of s-triazine compounds includes the following three steps:

[0034] Step 1: In the presence of alkaline reagents, 2,4,6-trichloropyrimidine or 2,4,6-trichloro-1,3,5-triazine and 4-substituted amino-1-benzoylpiperidine Intermediate M is obtained through nucleophilic substitution reaction in organic solvent;

[0035] Step 2: 2,6-Dichloro-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl)amino)-1,3,5-triazine or 2,6-di Chloro-4-(N-alkyl-N-(1-benzoyl-4-piperidinyl)amino)pyrimidine reacts with morpholine in an organic solvent to obtain intermediate N;

[0036] Step 3: Under the catalysis of palladium complex, intermediate N and substituted 3-pyrimidinyl boronic acid ester or substituted 5-pyrimidinyl boronic acid ester undergo Suzuki coupling to obtain product P.

[0037] The synthetic route is as follows:

[0038]

[0039] Wherein, the alkaline reagent is triethylami

[0061] Example 1: 2-(4-morpholinyl)-4-(2-amino-5-pyrimidinyl)-6-(N-cyclopropyl-N-(1-(3-fluorobenzoyl)- Synthesis of 4-piperidinyl))amino-1,3,5-triazine (compound 1)

[0062] step one:

[0063]

[0064] Add acetone (15mL) and 2,4,6-trichloro-1,3,5-triazine (0.61g) into a round bottom flask, cool to -10°C, and add 4-cyclopropylamino-1-( A mixture of 3-fluorobenzoyl)piperidine (0.90 g), triethylamine (TEA, 0.46 mL) and acetone (15 mL). After the addition was completed in about 30 minutes, the acetone was removed under reduced pressure, water (10 mL) was added to the residue, and extraction was performed twice with dichloromethane (20 mL). The extract was dried with anhydrous sodium sulfate and the solvent was removed to obtain intermediate M1 (oil).

[0065] Step two:

[0066]

[0067] Intermediate M1, morpholine, diisopropylethylamine and dichloromethane were added to a round bottom flask, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was directly mix

[0071] Example 2: 2-(4-morpholinyl)-4-(2-amino-5-pyrimidinyl)-6-(N-cyclopropyl-N-(1-(3-methylbenzoyl) -4-piperidinyl)) amino-1,3,5-triazine (compound 2) synthesis

[0072] Same as the synthesis of compound 1. Replace 4-cyclopropylamino-1-(3-fluorobenzoyl)piperidine with 4-cyclopropylamino-1-(3-methylbenzoyl)piperidine. The total yield of the three steps is 44%. EI-MS: 516 (M+H).