Structure of 949922-27-4
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| CAS No. : | 949922-27-4 |
| Formula : | C11H13NO |
| M.W : | 175.23 |
| SMILES Code : | CC(C1=CC2=C(CNCC2)C=C1)=O |
| English Name : | 1-(1,2,3,4-Tetrahydroisoquinolin-6-yl)ethanone |
| MDL No. : | MFCD20528277 |
| InChI Key : | WHFXFTCWKXJMBK-UHFFFAOYSA-N |
| Pubchem ID : | 57420565 |
* 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 |
|---|---|---|
| Stage #1: -butyl vinyl ether; 6-trifluoromethanesulfonyloxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester With 1,3-bis-(diphenylphosphino)propane; triethylamine In N,N-dimethyl-formamide at 80℃; for 7h; Stage #2: With water | 1.IV.4 To a stirred solution of 6-trifluoromethanesulfonyloxy-3,4-dihydro-lH-isoquinoIine- 2-carboxylicacid tert-butyl ester (3.81 g, 10 mmol) in dry DMF (30 ml) are added n- butylvinyl ether (6.01 g, 60 mmol, 6.0 eq.), TEA (1.67 ml, 12 mmol, 1.2 eq.), 1,3- bis(diphenylphosphino)propane (144 mg, 0.276 mmol, 0.0276 eq.), and palladium acetate (56.1 mg, 0.25 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 800C for 7 hr. Water (100 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml x 3). The combined organic layer is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (50 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basifed with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried with sodium sulfate and concentrated to give the title compound. MS (+VE) m/z 176.1 (M++.). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium carbonate; sodium iodide In acetonitrile at 20℃; | 1.IV.5 To a stirred solution of 6-acetyl- 1,2,3, 4-tetrahydroisoquinoline (350 mg, 2.0 mmol) in acetonitrile (10.0 ml) is added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (433 mg, 2.0 mmol, 1.0 eq.), K2CO3 (552 mg, 4.0 mmo], 2.0 eq.), and NaI (50 mg). The resulting mixture is stirred at rt overnight. Water (10.0 ml) is added to quench the reaction, and then the acetonitrile is evaporated. The residue is extracted with DCM (10 ml x 3). The combined organic phase is dried over sodium sulfate, and the solvent is removed under reduced pressure to give a residue that is purified by PTLC (EtOAc / 4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.68-7.74 (2H, m), 7.09 (IH, d), 3.74 (2H, s), 3.59~3.68(4H, m), 3.37 (2H, s), 2.94 (2H, t), 2.81 (2H, t), 2.68(1H, m), 2.57 (3H, s), 2.28 (4H, m), 1.60-2.10 (6H, m); MS (+VE) m/z 356.2 (M+ +1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 6-acetyl-1,2,3,4-tetrahydroisoquinoline With hydrogenchloride; water In ethyl acetate at 20℃; for 2h; Stage #2: With sodium carbonate In water; ethyl acetate | 1.IV.4 To a stirred solution of 6-trifluoromethanesulfonyloxy-3,4-dihydro-lH-isoquinoIine- 2-carboxylicacid tert-butyl ester (3.81 g, 10 mmol) in dry DMF (30 ml) are added n- butylvinyl ether (6.01 g, 60 mmol, 6.0 eq.), TEA (1.67 ml, 12 mmol, 1.2 eq.), 1,3- bis(diphenylphosphino)propane (144 mg, 0.276 mmol, 0.0276 eq.), and palladium acetate (56.1 mg, 0.25 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 800C for 7 hr. Water (100 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml x 3). The combined organic layer is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (50 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basifed with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried with sodium sulfate and concentrated to give the title compound. MS (+VE) m/z 176.1 (M++.). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 41.78% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1.5h; | 2 l-(l,2,3,4-Tetrahydroisoquinolin-6-yl)ethanone (500 mg, 2.8534 mmol), 1- bromomethyl-4-cyclopropylmethoxybenzene (826 mg, 3.4241 mmol) and K2CO3 (789 mg, 5.7068 mmol) were taken in DMF (10 ml) and stirred for 1.5 hrs at 7O0C. The reaction mixture was diluted with water and extracted with ethyl acetate twice. The organic extracts were washed with ice-cold water, brine and dried over anhydrous Na2SO^ The solvent was evaporated to obtain a crude residue. Purification of crude by column chromatography (silica gel 60-120 mesh, 1.5:8.5 EtOAc:hexane) afforded 400 mg (41.78%) of l-[2-(4-cyclopropylmethoxybenzyl)-l,2,3,4-tetrahydroisoquinolin-6- yl]ethanone. LCMS: [M+H]+ 336.2; IH-NMR (CDCl3): 7.675-7.699 (m, 2H), 7.266- 7.286 (d, 2H, J=8 Hz), 7.053-7.071(d, IH, J=7.2 Hz), 6.869-6.887 (d, 2H, J=7.2 Hz), 3.795-3.812 (d, 2H, J=6.8 Hz),3.646 (s, 4H), 2.940 (bs, 2H), 2.756-2.768 (m, 2H), 2.562 (s, 3H), 0.891-0.951 (m, IH), 0.636-0.653 (d, 2H, J=6.8 Hz), 0.355 (bs, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 62.85% | Stage #1: tert-butyl 6-acetyl-3,4-dihydroisoquinoline-2(1H)-carboxylate With hydrogenchloride In water; ethyl acetate at 20℃; for 8h; Stage #2: With sodium hydrogencarbonate In water Alkaline aqueous solution; | 6-Hydroxy-3,4-dihydro- lH-isoquinoline-2-carboxylic acid tert-butyl ester was converted to 6-acetyl-3,4-dihydro- lH-isoquinoline-2-carboxylic acid tert-butyl ester using the procedure reported in WO2007/106349. To a solution of 6-acetyl-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-butyl ester (1.25 g, 4.54 mmol) in ethyl acetate (20 ml) was added cone. HCl (10 ml) and the reaction mixture was stirred for 8 h at room temperature. The solvent was evaporated to obtain a crude residue which was dissolved in water and basified with NaHCO3. The aqueous solution was extracted with ethyl acetate twice and the combined extracts dried over anhydrous Na2SC^. The solvent was evaporated to obtain a crude residue. Purification of the crude residue by column chromatography (silica gel 60-120 mesh, MeOH:DCM 0.2:9.8) afforded (0.5 g, 62.85%) of l-(l,2,3,4-tetrahydroisoquinolin- 6-yl)ethanone. IH-NMR (DMSO-d6): 7.654 (bs, 2H), 7.124-7.143 (d, IH, J=7.6 Hz), 3.871 (s, 2H), 2.921-2.948 (t, 2H, J=5.6 Hz), 2.733-2.746 (m, 2H),2.517 (s, 3H). |
| With trifluoroacetic acid In dichloromethane at 20℃; for 6h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine / ethyl acetate / 0 - 60 °C 2.1: ethanol / 0.67 h / 50 °C / Molecular sieve 2.2: 4 h |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine / ethyl acetate / 0 - 60 °C 2.1: ethanol / 0.67 h / 50 °C / Molecular sieve 2.2: 4 h 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 0.33 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 0 - 60℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: 1-chloro-1-(dimethylamino)-2-methyl-1-propene / dichloromethane / 2 h / 20 °C 1.2: 14 h / 20 °C 2.1: tetrahydrofuran / 1.25 h / 20 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 6 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: tetrahydrofuran / 1.25 h / 20 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 6 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium fluoride In dimethyl sulfoxide at 110℃; for 15h; | 128.C Step C. 5-(6-acetyl-3,4-dihydroisoquinoiin-2(IH)-yi)-3-methyl- I -(p-tolyi}- I 1-I- pyrazole-4-carhonitrile: A solution of potassium fluoride (0.663 g, 11.41 mmoi), 5-iodo-3-inethyi-1-(p-tolyl)- IH-pyrazole-4-carbonitrile (1.844 g, 5.71 mniol) andi-(i,2.3,4-tetrahydroisoquinolin-6-yl)ethanone (1.00 g, 5.71 mmoi) in DMSO (15 ml) was stirred at 110°C for 15 h. The reaction was quenched with water, extracted with EtOAc (3x30 mE). The organic layers were washed with water (2x15 mL) and brine (2x1 5 mE), dried over Na2SO4 and filtered. The filtrate was concentrated in vcicuo and purified by silica gel chromatography (PE:EtOAc=30: l3: 1) to give the title compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1.1: potassium fluoride / dimethyl sulfoxide / 15 h / 110 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 6 h / 0 - 20 °C 3.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 3 h / 20 °C 4.1: palladium on activated charcoal; hydrogen / methanol / 15 h / 10 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1.1: potassium fluoride / dimethyl sulfoxide / 15 h / 110 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 6 h / 0 - 20 °C 3.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 3 h / 20 °C 4.1: palladium on activated charcoal; hydrogen / methanol / 15 h / 10 °C 5.1: ammonium hydroxide / methanol; carbon dioxide / 38 °C / Supercritical conditions; Resolution of racemate; liquid CO2 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: potassium fluoride / dimethyl sulfoxide / 15 h / 110 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 6 h / 0 - 20 °C |

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