1,1a,6,6a-tetrahydrocycloprop[a]indene-1-amine derivatives and preparation method and applications thereof
A technology of amine derivatives and cyclopropanes, which is applied in the preparation of carboxylic acid amides, the preparation of amino compounds, the preparation of organic compounds, etc., can solve the problems of low inhibitory activity and poor selectivity.
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Embodiment 1
[0251] Example 1: Preparation of (trans)-1,1a,6,6a-tetrahydrocyclopropane[a]inden-1-amine (1)
[0252] (a) Ethyl (trans)-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylate (1a) and (cis)-1,1a,6,6a-tetrahydrocyclo Preparation of ethyl propane[a]indene-1-carboxylate (1a')
[0253] Indene (3.42g, 26.30mmol) and rhodium acetate dimer (115mg, 0.26mmol) were added to 50mL of dichloromethane, ethyl diazoacetate (2.0mL, 39.45mmol) was added under reflux, and the solution Stir at 45°C for 3 hours, then overnight at room temperature, remove the solvent in vacuo, and purify by silica gel column chromatography (petroleum ether / ethyl acetate=100:1) to give 1a and 1a' as colorless oils, 3.35g (59 %), directly used in the next step reaction.
[0254] (b) tert-butyl (trans)-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carbamate (1b) and (cis)-1,1a,6,6a-tetrahydro Preparation of tert-butyl cycloprop[a]indene-1-carbamate (1b')
[0255] 1a and 1a' (3.35g, 15.49mmol) were added to 20mL MeOH, ...
Embodiment 2
[0258] Embodiment 2: the preparation of (cis)-1,1a,6,6a-tetrahydrocyclopropane[a]inden-1-amine (2)
[0259] The preparation method of 2 was the same as that of 1 in Example 1, except that 1b' (300mg, 1.16mmol) was used instead of 1b to obtain 2, a yellow solid, 213mg (94%). 1 H NMR (400MHz, Methanol-d 4 )δ7.38–7.35(m,1H),7.20–7.13(m,3H),3.26(d,J=6.9Hz,1H),3.09(d,J=17.7Hz,1H),2.85(dt,J =7.3,1.6Hz,1H),2.22(tdd,J=7.0,2.5,0.9Hz,1H),2.04(t,J=2.1Hz,1H). 13 C NMR (101MHz, Methanol-d 4 )δ143.1, 142.7, 128.1, 127.8, 126.3, 125.1, 37.0, 35.4, 30.6, 22.7.
Embodiment 3
[0260] Example 3: Preparation of (trans)-N-(2-methoxybenzyl)-1,1a,6,6a-tetrahydrocyclopropane[a]inden-1-amine (3)
[0261] 1 (50 mg, 0.26 mmol) was dissolved in 2.0 mL MeOH at room temperature and triethylamine (39 mg, 0.39 mmol) was added to give the free amine. Then 2-methoxybenzaldehyde (35mg, 0.26mmol) was added to the solution, magnetically stirred for 30min, 4A molecular sieves were added, stirred for 15min, sodium borohydride (30mg, 0.78mmol) was added, and reacted for 16 hours. The mixture was then filtered and the solvent removed in vacuo to give the crude product, dissolved in ethyl acetate, saturated NaHCO 3 Wash, collect the organic phase, anhydrous Na 2 SO 4 It was dried, filtered and concentrated in vacuo, and purified by silica gel column chromatography (petroleum ether / ethyl acetate=4:1) to give 3, yellow oil, 26 mg (40%). 1 H NMR (400MHz, Chloroform-d) δ7.25–7.17(m,3H),7.11–7.01(m,3H),6.91–6.83(m,2H),3.96–3.79(m,5H),3.15(dd ,J=17.0,7.0Hz,1H),2.91(d,J=17.1H...
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