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Chemical Structure| 166398-33-0 Chemical Structure| 166398-33-0

Structure of 166398-33-0

Chemical Structure| 166398-33-0

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Product Details of [ 166398-33-0 ]

CAS No. :166398-33-0
Formula : C15H18N2O2
M.W : 258.32
SMILES Code : CC(C)(C)OC(=O)N1CCC2=C(C1)C=CC(=C2)C#N
English Name :tert-Butyl 6-cyano-3,4-dihydroisoquinoline-2(1H)-carboxylate
MDL No. :MFCD11043755

Safety of [ 166398-33-0 ]

Application In Synthesis of [ 166398-33-0 ]

* 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.

  • Downstream synthetic route of [ 166398-33-0 ]

[ 166398-33-0 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 557-21-1 ]
  • [ 158984-84-0 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 80℃; for 0.75h; Yield given;
In N,N-dimethyl-formamide at 80℃; for 18h; 60 Example 60 t-butyl 6-cyano-3,4-dihydro-2(1H)-isoquinolinecarboxylate: To a solution of the compound (0.56 g) prepared in Example 59 in N,N-dimethylformamide (3 mL), zinc cyanide (173 mg) and tetrakis(triphenyl)phosphine palladium (173 mg) were added, followed by stirring at 80°C for 18 hours. The reaction mixture was added with a saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with t-butyl methyl ether. The organic layer was washed with water, dried and concentrated. Thus, the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 1:0 to 3:1) to thereby give the title compound (130 mg) having the following physical properties. TLC: Rf 0.36 (hexane:ethyl acetate = 3:1)
  • 3
  • [ 24424-99-5 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 61 percent / Et3N / tetrahydrofuran; H2O / Ambient temperature 2: Et3N / CH2Cl2 / 0 °C 3: palladium tetrakistriphenylphosphine / dimethylformamide / 0.75 h / 80 °C
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2.16 h / 0 - 20 °C 2: triethylamine / dichloromethane / 2.16 h / 0 - 20 °C 3: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 3 h / Reflux
Multi-step reaction with 2 steps 1: dichloromethane / 2 h / 20 °C 2: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 1.5 h / 150 °C / Sealed tube
  • 4
  • [ 59839-23-5 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 61 percent / Et3N / tetrahydrofuran; H2O / Ambient temperature 2: Et3N / CH2Cl2 / 0 °C 3: palladium tetrakistriphenylphosphine / dimethylformamide / 0.75 h / 80 °C
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2.16 h / 0 - 20 °C 2: triethylamine / dichloromethane / 2.16 h / 0 - 20 °C 3: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 3 h / Reflux
  • 5
  • [ 158984-83-9 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / 0 °C 2: palladium tetrakistriphenylphosphine / dimethylformamide / 0.75 h / 80 °C
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2.16 h / 0 - 20 °C 2: tetrakis-(triphenylphosphine)-palladium / N,N-dimethyl-formamide / 3 h / Reflux
Multi-step reaction with 2 steps 1: pyridine / 0.5 h / 0 °C 2: tetrakis-(triphenylphosphine)-palladium / N,N-dimethyl acetamide / 16 h / 80 °C / Inert atmosphere
  • 6
  • [ 770697-94-4 ]
  • [ 158984-84-0 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
23% With tetrakis-(triphenylphosphine)-palladium In N,N-dimethyl-formamide for 3h; Reflux;
18.3 g With tetrakis-(triphenylphosphine)-palladium In N,N-dimethyl-formamide at 80 - 100℃; for 5h;
With tetrakis-(triphenylphosphine)-palladium In N,N-dimethyl acetamide at 80℃; for 16h; Inert atmosphere; Tert-butyl 6-cyano-3,4-dihydroisoquinoline-2(1H)-carboxylate (12-12c). To a solution of tert-butyl 6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydroisoquinoline-2(1H)- carboxylate (12-12b, 900 mg, 2.36 mmol, 1 eq) in DMF (5 mL) was added Zn(CN)2 (554.25 mg, 4.72 mmol, 299.60 uL, 2 eq) and Pd(PPh3)4 (272.70 mg, 235.99 umol, 0.1 eq) at 20°C under N2. The mixture was stirred at 80°C for 16 hours. TLC (Petroleum ether: Ethyl acetate = 3:1) showed 12-12b was consumed completely. The mixture was filtered and the filtrate was washed with water (40 mL*2). The mixture was extracted with MTBE (40 mL *2). The combined organic layers were washed with brine (30 mL*3), dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The filter cake was quenched by NaClO(aq)(50 ml). The residue was purified by column chromatography (SiO2, Petroleum ether:Ethyl acetate=5:1 to 2:1) to give 12-12 was obtaind as a white solid.1H NMR (400 MHz, CDCl3-d) 7.45-7.45 (m, 1H), 7.50-7.43 (m, 1H), 7.21 (d, J = 7.8 Hz, 1H), 4.62 (s, 2H), 3.67 (br t, J = 5.8 Hz, 2H), 2.87 (br t, J = 5.7 Hz, 2H), 1.50 (s, 9H)
  • 8
  • [ 24424-99-5 ]
  • [ 166398-34-1 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
96% With triethylamine In dichloromethane at 20℃; for 1h;
96% With triethylamine In dichloromethane at 20℃; for 1h;
81.7% With triethylamine In dichloromethane at 0 - 20℃; for 6h; Inert atmosphere; Step 1: Tert-butyl 6-cyano-3,4-dihydroisoquinoline-2(1H)-carboxylate (2) To a solution of 1,2,3,4-tetrahydroisoquinoline-6-carbonitrile (120 mg, 0.76 mmol) in DCM (3 mL) was added (Boc)2O (248 mg, 1.15 mmol) followed by TEA (0.21 mL, 1.52 mmol) at 0 °C and the mixture was stirred at room temperature for 6 hours. The mixture was diluted with water and extracted with DCM twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 30% EtOAc in PE) to give the title compound (160 mg, yield 81.7%) as a white solid. LC/MS (ESI) m/z: 259 (M+H)+.
With triethylamine In dichloromethane at 25℃; for 1h; Di-tert-butyl dicarbonate (2.23ml, 9.6 mmol) was added to a mixture of 1 ,2,3,4- tetrahydro-6-isoquinolinecarbonitrile (Preparation 166) (1.38g, 8.7 mmol) and triethylamine (3.65ml, 26 mmol) in DCM (25ml) and the mixture was stirred at room temperature for 60min at 25°C. The solution was washed with water (25ml) and dried (MgSO4). The solvent was evaporated and the residue was dissolved in DCM and loaded onto a silica cartridge. The cartridge was eluted with an ethyl acetate / cyclohexane gradient (10-50%). The appropriate fractions were combined and evaporated in vacuo to give 1 ,1-dimethylethyl 6-cyano-3,4-dihydro-2(1 H)- isoquinolinecarboxylate (2.17g) as a colourless solid.LCMS (Method formate): Retention time 1.17min, MH+ = 259

  • 9
  • [ 166398-33-0 ]
  • [ 1258856-46-0 ]
YieldReaction ConditionsOperation in experiment
98% With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol at 80℃; for 4h;
98% With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol at 80℃; for 4h;
With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol at 80℃; for 4h; Hydroxylamine hydrochloride (3.5Og, 50 mmol) was added to a suspension of 1 ,1- dimethylethyl 6-cyano-3,4-dihydro-2(1 H)-isoquinolinecarboxylate (Preparation 165) (2.17g, 8.4 mmol) and sodium hydrogen carbonate (4.23g, 50 mmol) in ethanol (100ml) and the mixture heated at 800C for 4h. The cooled mixture was filtered and the filtrate evaporated to give 1 ,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-3,4- dihydro-2(1 H)-isoquinolinecarboxylate as a colourless foam (2.78g). LCMS (Method formate): Retention time 0.70min, MH+ = 292
  • 10
  • [ 226942-29-6 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 1 h / 130 °C / Irradiation with microwave 2: triethylamine / dichloromethane / 1 h / 25 °C
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 1 h / 130 °C / Microwave irradiation 2: triethylamine / dichloromethane / 1 h / 20 °C
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 1 h / 130 °C / Microwave irradiation 2: triethylamine / dichloromethane / 1 h / 20 °C
Multi-step reaction with 2 steps 1: dichloromethane / 2 h / 20 °C 2: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 1.5 h / 150 °C / Sealed tube

  • 11
  • [ 166398-33-0 ]
  • [ 1258856-45-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium hydrogencarbonate / ethanol / 4 h / 80 °C 2: pyridine / toluene / 2.33 h / 20 - 120 °C / Inert atmosphere
 

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