Azaindole compound and application thereof
A technology of azaindole and compounds, applied in the field of medicinal chemistry, can solve problems such as non-existence and side effects
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[0096] Example 1: Synthesis of compounds 5a-5j
[0097]
[0098] Synthesis of Intermediate 4a:
[0099]
[0100] Put NaH (192mg, 4.8mmol) in the reaction flask, replace the nitrogen, add 7mL of anhydrous DMF to dissolve, add methyl phosphonoacetate diethyl under the condition of ice-water bath, stir for 0.5 hours, add compound 3a( 636mg, 3.973mmol) in 7.5mL DMF solution, stirred at room temperature for 8 hours. Sampling point plate, the reaction is almost complete, add water to quench the reaction, stir for 2 hours, extract three times with ethyl acetate, wash with saturated brine, dry and filter, concentrate and purify by silica gel column to obtain yellow solid compound n1 (520mg, 60.5%); n1 (520mg, 2.4mmol) dissolved in THF / MeOH / H 2 To the O (5mL / 8mL / 8mL) mixed solution, NaOH (288mg, 7.2mmol) was added and stirred at room temperature for 4 hours. Sampling point board, the reaction is basically completed. Add HCl (1M) to adjust the pH=5.0, and filter to obtain Intermediate 4a ...
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[0166] Example 2: Synthesis of Compound 9
[0167]
[0168] Compound 6 (208mg, 1mmol) and AlCl 3 (667mg, 5mmol) was placed in a reaction flask, replaced with nitrogen, dissolved with 20mL of DCM, and stirred at room temperature for 1 hour. Add methyl 2-chloro-2-oxoacetate (122mg, 1mmol), stir at 0°C for 0.5 hours, then warm to room temperature, and add 2 Stir overnight under protected conditions. Sampling point plate, the reaction is almost complete, extraction, DCM extraction three times, combined organic phases, dried, filtered, concentrated, and purified by silica gel column chromatography to obtain yellow solid compound 7 (270mg, 92%); 1 H NMR(400MHz, CDCl 3 )δ8.71(d,J=7.8Hz,1H), 8.49(d,J=4.7Hz,1H), 7.63–7.53(m,3H), 7.48(d,J=5.7Hz,2H), 7.35( dd,J=7.8,4.8Hz,1H), 3.74(s,3H), 3.24(s,3H). 13 CNMR(100MHz, CDCl 3 )δ177.5, 162.6, 149.1, 144.0, 137.7, 132.1, 119.8, 119.2, 112.7, 52.9.
[0169] Compound 7 (270 mg, 0.92 mmol) and LiOH (66 mg, 2.76 mmol) were put in the reaction flask, a...
Example Embodiment
[0171] Example 3: Synthesis of Compound 12
[0172]
[0173] Put NaH (112mg, 2.8mmol) in the reaction flask, replace the nitrogen, add 5mL anhydrous DMF to dissolve, add methyl phosphonoacetate diethyl (555mg, 2.2mmol) under ice-water bath conditions, stir for 0.5 hour, A DMF solution of compound 10 (451 mg, 2.0 mmol) was added dropwise and stirred at room temperature for 8 hours. Sampling point plate, the reaction is almost complete, add water to quench the reaction, stir for 2 hours, extract three times with ethyl acetate, wash with saturated brine, dry, filter, concentrate, and purify by silica gel column to obtain yellow intermediate n7 (542 mg, 84%).
[0174] Intermediate n7 (542mg, 1.68mmol) was dissolved in CH 2 Cl 2 (9mL) and TFA (2mL) mixed solution, stirred overnight at room temperature, sampling spots, the reaction is almost complete, to obtain compound 11 (550mg, crude).
[0175] To the DMF (3.5mL) solution of compound 11 (150mg, 0.565mmol) and TEA (0.5mL, 3.6mmol) was a...
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