A kind of isoquinoline compound, its intermediate, preparation method and application
A technology of isoquinoline and compounds, applied in the field of isoquinoline compounds, can solve the problems of needing improvement of specificity and weak signal of developer, etc., and achieve the effect of good binding ability
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Embodiment 1
[0136] The preparation of embodiment 1 compound II-B---II-D
[0137]
[0138] General synthesis procedure: 1.0 mmol substrate 6, 5N CsF or NaNH under anhydrous and anaerobic conditions 2 , 5.0 mL DMF, and the reaction mixture was heated to 140-150° C. and stirred until the reaction was completed (the reaction time was 12 h, and the reaction was monitored by TLC or HPLC). The reaction mixture was separated between ethyl acetate and saturated brine (the amount of ethyl acetate and saturated brine used were both 200 mL), the organic phase was dried over magnesium sulfate, and the solvent was drained. The crude product was separated on a silica gel column using ethyl acetate and methanol (95:5, v / v) as mobile phase.
[0139] Compound II-B, yield 65%, purity>95%, 1 H NMR (400MHz; CDCl 3 ),δ9.19(s,1H,Ar-H),8.01(s,1H,Ar-H),7.88(d, 3 J HH =8.9Hz,1H,Ar-H),7.57(d, 3 J HH =8.9Hz,1H,Ar-H),7.24(m,1H,Ar-H).
[0140] Compound II-C, yield 47%, purity > 85%, 1 H NMR (400MHz; CDCl ...
Embodiment 2
[0142] The preparation of embodiment 2 compound II-C---II-D series
[0143]
[0144] Compound II-C synthesis steps: 1.0mmol substrate, 10N NaOCH 3 , 5.0 mL CH 3 OH, the reaction mixture was reacted at 80°C for 22 hours, and then washed with 20N H 2 SO 4 Neutralize the acidification and stir until the reaction is complete. The reaction mixture was partitioned between ethyl acetate and saturated brine. The organic solvent phase was dried in magnesium sulfate, and the solvent was drained, and the crude product was separated on a silica gel column, using ethyl acetate and methanol (95:5, v / v) as the mobile phase.
[0145] Compound II-D synthesis steps: 1.0 mmol substrate, 10N H 2 o 2 , 5.0 mL CHCl 3 , and the reaction mixture was stirred at 70 °C until the reaction was complete. The reaction mixture was partitioned between ethyl acetate and saturated brine. The organic solvent phase was dried in magnesium sulfate, and the solvent was drained, and the crude product was ...
Embodiment 3
[0146] The preparation of embodiment 3 compound II-E---II-G
[0147]
[0148] General synthesis procedure: 1.0 mmol substrate VI-A, 2.0 N (CF 3 CO) 2 O, 4.0N DABCO, 5.0mL CH 2 Cl 2 , and the reaction mixture was stirred at room temperature until the reaction was complete. Add excess K 2 CO 3 Solid, stirred for 1 ~ 2h, then filtered. The reaction mixture was added dropwise to 10 times the volume of diethyl ether, and the mixture was allowed to stand overnight. The solution was partially decanted and the solid was washed with diethyl ether. The solid was dissolved in 5.0 mL THF and 2.0N Bu 4 NF solution, the reaction mixture was stirred at 60 °C until the reaction was complete. The solvent was drained, and the crude product was separated with a silica gel column, using ethyl acetate and hexane (80:20, v / v) as the mobile phase.
[0149] Compound II-E, yield 78%, purity>95%, 1 H NMR (400MHz; CDCl 3 ),δ8.28-8.30(m,2H,Ar-H),7.88(d, 3 J HH =8.9Hz,1H,Ar-H),7.24(d, 3 ...
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