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CAS No. :138113-09-4 MDL No. :MFCD09744147
Formula : C13H15NO Boiling Point : -
Linear Structure Formula :- InChI Key :YXDUMIVUPSVYLB-UHFFFAOYSA-N
M.W : 201.26 Pubchem ID :11052667
Synonyms :

Safety of [ 138113-09-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H317-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 138113-09-4 ]

* 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 [ 138113-09-4 ]

[ 138113-09-4 ] Synthesis Path-Downstream   1~93

  • 1
  • [ 93189-18-5 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride; diethyl ether
  • 2
  • [ 138113-08-3 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
95% With ammonia; hydrogen; In ethanol; water; at 60℃; under 228015 Torr; for 12h;Autoclave; Reference example 6: The preparation of 2-(7-methoxy-1-naphthyl)ethylamine 56g 7-methoxy-1-naphthaleneacetonitrile, 120ml ammonia water, 332ml 95% ethanol, 20g Raney-Ni were added into autoclave. H2 was introduced after vacuuming it. The operation was repeated for 3 times. The reaction was stirred for 12 hours while H2 was introduced and the condition of 300 atm and 60C was maintained. After completion of the reaction, the reaction was kept overnight at room temperature. On the next day, it was vacuumed and N2 gas was introduced. The autoclave was opened up, and the reaction solution was filtered to remove the catalyst. The filtrate was vacuum evaporated until dry to obtain 56g light green oil. The content is measured as 96.95% by HPLC, and the yield is 95%.
92% With hydrogen; ammonium hydroxide;nickel; In methanol; at 20℃; under 3102.97 Torr; for 20h; Step 7 2-(7-Methoxy-naphthalen-1-yl)-ethylamine: At ambient temperature and under a pressurized hydrogen atmosphere (60 psi), a mixture of (7-methoxy-naphthalen-1-yl)acetonitrile (1.6 g; 8.1 mmol), Raney nickel (0.5 g) in methanol (80 mL), and ammonium hydroxide (5 mL) was continuously stirred for about 20 hours. The catalyst was then removed by filtration and the filtrate was concentrated to give the title product as a yellow oil, which was used directly in the next step without further purification (1.5 g, yield 92%). 1H NMR (300 MHz, CD3OD): delta 3.00 (br. s, 2H), 3.20 (br. s, 2H), 3.93 (s, 3H), 7.12 (d, J=8.7 Hz, 1H), 7.24 (m, 3H), 7.63 (d, J=7.8 Hz, 1H), 7.73 (d, J=8.7 Hz, 1H). LC-MS: 202 (M+H)+.
71.2% With ammonia; hydrogen; In ethanol; at 45℃; under 15001.5 Torr;Green chemistry; A hydrogenation reaction vessel was charged with <strong>[138113-08-3](7-methoxy-1-naphthyl)acetonitrile</strong> (10.0 g, 50.7 mmol), added to a 500 ml hydrogenreaction vessel, dissolved in 200 ml of anhydrous ethanol, and 0.95 g of Raney nickel wasadded to thehydrogenation reaction. kettle introducing gaseous ammonia, ammonia gas stream flatstable holding 0.1-5h; 1-5 times and then replaced by hydrogen, a sealed reactor; hydrogenation reactor was placed 45 C, 2.0MPa bar hydrogen pressureand stirred overnight under member; the reaction was monitored by TLC until complete; the reaction solution was decanted, suction filtered, rinsed with a little 95% ethanol; filtrate concentratedsolution has a pH, and dissolved in ethyl acetate, hydrochloric acid gas was introduced, the control of the mother liquor is 8.0 to 9.0, a large number of white precipitate heavyprecipitate Suction suspension was filtered off, the filter cake was washed with ethyl acetate, and the filter cake was dried at 50 C. to obtain an off-white solid, ie compound (II) 8.7 g, yield 71.2%, product properties: white powder.Purity: 99.52%.
With ammonia; hydrogen;nickel; In ethanol; water; at 40℃; under 22502.3 Torr; There are introduced into a 1100 litre reactor 80.0 kg of the compound obtained in Step B, 24.0 kg of Raney nickel in ethanol and 170 l of ammonium hydroxide. The mixture is stirred under a hydrogen pressure of 30 bars, then brought to 40 C. When all the starting substrate has disappeared, the solvent is evaporated off, the resulting residue is redissolved in ethyl acetate, and 41.5 l of an 11N hydrochloric acid solution are added. After filtration, the precipitate obtained is washed with ethyl acetate and then dried in an oven to give the title product in a yield of 95.3% and with a chemical purity exceeding 99.5%. Melting point: 243 C.
With sodium tetrahydroborate; di-tert-butyl dicarbonate; nickel dichloride; In methanol; for 12h; A mixture of 2-(7-methoxynaphthalen-1-yl) acetonitrile (compound 2,1.99 g, 10.0 mmol), sodiumborohydride (417mg, 11.0 mmol), nickelchloride(475 mg, 5.0 mmol) and dibutyldicarbonate (0.2 mL) in 20 mL methanol were stirred at room temperature for 12 h, then the reaction was suspended with 20 mL water. The resulting mixture was concentrated under reduced pressure, then 20 mL water was added, extracted with ethyl acetate(20 mL×3), the combined organic layer were concentrated under reduced pressure. After that 10 mL trifluoroacetic acid and 10 mL dichloromethane were added, stirred at room temperature for 4 h and adjust to pH=12, then washed with water (20 mL×3) and compound 3 was obtained after concentrated under reduced pressure.
With ammonia; hydrogen; In ethanol; at 30 - 40℃; under 2250.23 - 3000.3 Torr; for 24h;Autoclave; To the autoclave was charged 30 g of (7-methoxy-1-naphthyl) acetonitrile prepared in Example 19, 7.5 g of Raney nickel,95% ethanol 200ml, ammonia 60ml, autoclave sealed, nitrogen replacement, access to hydrogen,Control the pressure of 0.3-0.4Mpa, temperature 30-40 , holding pressure after 24 hours, cooling, remove the reaction solution, filter recovery Raney nickel, the filtrate evaporated under vacuum (7-methoxy-1-naphthyl) Ethylamine oil;To the oil was added 120 ml of toluene, 25 ml of triethylamine was stirred and dissolved,Control temperature below 30 add acetic anhydride 17ml, and 0-10 incubation reaction 30min,Then, 120 ml of water was added dropwise and cooled to 0-5 C for 2 h. The mixture was filtered and dried to give 31 g of aggamatine, the yield was 83.8% and the HPLC purity was 99.9%.

  • 3
  • [ 138113-09-4 ]
  • [ 138112-76-2 ]
YieldReaction ConditionsOperation in experiment
With sheep pineal supernatant (serotonin-N-acetyl transferase); Pargyline In phosphate buffer at 37℃; for 0.166667h;
  • 4
  • [ 138113-09-4 ]
  • [ 79-03-8 ]
  • [ 138112-79-5 ]
YieldReaction ConditionsOperation in experiment
1.41 g With triethylamine In dichloromethane at 0 - 20℃;
  • 5
  • [ 625-38-7 ]
  • [ 138113-09-4 ]
  • but-3-enoic acid [2-(7-methoxy-naphthalen-1-yl)-ethyl]-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at -20 - 20℃;
  • 6
  • [ 139525-77-2 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In water; at 10 - 30℃; for 0.75h; Example-9: Preparation of (7-Methoxy-l-naphthyI)ethanamine in solid formTo 50g. (0.21 mol.) of (7-Methoxy-l-naphthyl) ethanamine hydrochloride solution in250 ml. water present in a clean and dry R.B.Flask 5 gr. of charcoal was charged. The reaction mixture was stirred at about 30°C for about 15 min. and then filtered on a celite bed. Sodium carbonate (34 gr., 0.32 mol) was added to the filtrate obtained. Then the reaction mixture was stirred at about 30°C for about 15 min. and further cooled to about 10°C for about 30 min. The separated solid was filtered and the solid obtained was washed with 50 ml. of distilled water. 70 ml. of ethyl acetate was added to the wet solid and stirred at about 0 °C for about 30 min. The solid obtained was filtered and rinsed with ethyl acetate to afford 30 g. of the title compound.M. R.: 101-104 °C. Purity by H.P.L.C: 99.85percent.
  • 7
  • [ 138113-09-4 ]
  • [ 98-88-4 ]
  • [ 138112-87-5 ]
YieldReaction ConditionsOperation in experiment
In water; ethyl acetate at 0 - 20℃;
  • 8
  • [ 138113-09-4 ]
  • [ 3024-72-4 ]
  • 3,4-dichloro-<i>N</i>-[2-(7-methoxy-naphthalen-1-yl)-ethyl]-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water; ethyl acetate at 0 - 20℃;
  • 9
  • [ 138113-09-4 ]
  • [ 814-68-6 ]
  • <i>N</i>-[2-(7-methoxy-naphthalen-1-yl)-ethyl]-acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water; ethyl acetate at 0 - 20℃;
  • 10
  • [ 138113-09-4 ]
  • [ 103-80-0 ]
  • [ 138112-77-3 ]
YieldReaction ConditionsOperation in experiment
In water; ethyl acetate at 0 - 20℃;
  • 11
  • [ 138113-09-4 ]
  • [ 5006-22-4 ]
  • [ 138113-13-0 ]
YieldReaction ConditionsOperation in experiment
37% With triethylamine In dichloromethane at 50℃; for 4h;
  • 12
  • [ 138113-09-4 ]
  • [ 6831-55-6 ]
  • 2-(3,4-dichloro-phenyl)-<i>N</i>-[2-(7-methoxy-naphthalen-1-yl)-ethyl]-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water; ethyl acetate at 0 - 20℃;
  • 13
  • [ 59081-65-1 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90.7 percent / DDQ / CH2Cl2 / 20 °C 2: 88.2 percent / TsOH*H2O / benzene / 1 h / Heating 3: LiAlH4 / tetrahydrofuran / 45 - 50 °C
  • 14
  • [ 6836-19-7 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 95 percent / n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 2: 90.7 percent / DDQ / CH2Cl2 / 20 °C 3: 88.2 percent / TsOH*H2O / benzene / 1 h / Heating 4: LiAlH4 / tetrahydrofuran / 45 - 50 °C
Multi-step reaction with 7 steps 1.1: zinc / iodine / toluene / Reflux 1.2: Reflux 1.3: 3 h / Reflux 2.1: sulfur / ethyl acetate / 10 h / 215 °C 3.1: sodium hydroxide; water / ethanol / 3 h / 20 °C 4.1: thionyl chloride / dichloromethane / 2 h / Reflux 5.1: ammonia / ethyl acetate; water / Cooling with ice 6.1: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 7.1: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave
Multi-step reaction with 3 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 0.5 h / 15 °C 1.2: 10 - 15 °C 2.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 13 h / Reflux 3.1: ammonium hydroxide; hydrogen / ethanol / 8 h / 40 - 45 °C / 3750.38 - 4500.45 Torr / Autoclave
Multi-step reaction with 3 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 0.5 h / 15 °C 1.2: 10 - 15 °C 2.1: chloranil / 13 h / Reflux 3.1: ammonium hydroxide; hydrogen / ethanol / 7 h / 40 - 50 °C / 3000.3 - 3750.38 Torr / Autoclave
Multi-step reaction with 3 steps 1.1: sodium hydride / 1,2-dimethoxyethane / 0.5 h / 15 °C 1.2: 10 - 15 °C 2.1: chloranil / 13 h / Reflux 3.1: ammonium hydroxide; hydrogen / ethanol / 7 h / 50 - 55 °C / 5250.53 - 6000.6 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 20 - 30 °C 3: toluene / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 18 h / 30 - 40 °C 3: acetic acid / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 18 h / 30 - 40 °C 3: acetic acid / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 10 - 20 °C 3: acetic acid / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 15 h / 10 - 20 °C 3: formic acid / toluene / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 20 h / 30 - 40 °C 3: acetic acid / toluene / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 10 - 20 °C 3: butyric acid / ethyl acetate / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 24 h / -20 - -10 °C 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 40 - 50 °C 3: acetic acid / toluene / 12 h / Reflux 4: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave

Reference: [1]Chu; Li [Synthetic Communications, 2001, vol. 31, # 4, p. 621 - 629]
[2]Current Patent Assignee: TIANJIN TAIPU PHARMACEUTICAL SCIENCE TECHNOLOGY - EP2474522, 2012, A1
[3]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI SYNERGY PHARMACEUTICALS - EP2921473, 2015, A1
[4]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI SYNERGY PHARMACEUTICALS - EP2921473, 2015, A1
[5]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI SYNERGY PHARMACEUTICALS - EP2921473, 2015, A1
[6]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[7]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[8]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[9]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[10]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[11]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[12]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
[13]Current Patent Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO., LTD.; JIANGXI TONGHE PHARMACEUTICAL - CN104803882, 2017, B
  • 15
  • [ 360766-78-5 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 88.2 percent / TsOH*H2O / benzene / 1 h / Heating 2: LiAlH4 / tetrahydrofuran / 45 - 50 °C
  • 16
  • [ 138113-09-4 ]
  • [ 866262-28-4 ]
YieldReaction ConditionsOperation in experiment
With ammonia; lithium; <i>tert</i>-butyl alcohol In tetrahydrofuran at -78℃; for 1.5h; 1.1 STEP 1 ; 2-(7-METHOXY-5,8-DIHYDRONAPHTHALEN-1-YL) ETHANAMINE; To a tetrahydrofuran (10 ml) solution of 2- (7-methoxy-1-naphthyl) ethanamine (0. 9 g, 4. 47 mmol) (prepared according to Synthetic Communications, 31 (4), p 621- 629 (2001) ) and t-buthanol (1.0 g, 13.4 mmol) were added liq. NH3 (100 ml) at- 78 °C. To the mixture was added Li wire (93.0 mg, 13.4 mmol) over 30 min. at- 78 °C and stirred for lh at-78 °C. Methanol/water (3: 1) co-solvent (30ml) was added to this mixture to stop the reaction and additional stirring was allowed for 16h to evaporate ammonia. The obtained residue was partitioned with ethylacetate and water. Then organic layer was separated, washed with water, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 2- (7-methoxy-5, 8- dihydronaphthalen-1-yl)-ethanamine (crude 0.83 g) which was used for next reaction without further purification. Yellow colored oil. MS (ESI) m/z 204 (M + H) +.
  • 17
  • [ 138113-09-4 ]
  • [ 139525-77-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water; ethyl acetate; There are introduced into a 1100 litre reactor 80.0 kg of the compound obtained in Step B, 24.0 kg of Raney nickel in ethanol and 170 l of ammonium hydroxide. The mixture is stirred under a hydrogen pressure of 30 bars, then brought to 40° C. When all the starting substrate has disappeared, the solvent is evaporated off, the resulting residue is redissolved in ethyl acetate, and 41.5 l of an 11N hydrochloric acid solution are added. After filtration, the precipitate obtained is washed with ethyl acetate and then dried in an oven to give the title product in a yield of 95.3percent and with a chemical purity exceeding 99.5percent. Melting point: 243° C.
With hydrogenchloride; In ethyl acetate; at 20℃; for 2h; Example 5: Preparation of 2-(7-methoxynaphthalen-1 -yl) ethanamine hydrochloride (formula Vila)Borane-DMS (106 gm) was added to a stirred solution of 2-(7-methoxynaphthalen-1 - yl) acetamide (1 00 gm) and toluene (500 ml) at room temperature. The reaction mixture was heated and maintained at 80-85 °C until reaction completes. The reaction mixture was cooled to room temperature. The reaction mass was slowly quenched into 10percent HCI. Solvent was evaporated and Ethyl acetate (50 ml) was added. pH was adjusted to 12 using NaOH solution. The organic layer was separated and washed with water and dried over sodium sulphate. The organic layer was evaporated to dryness under reduced pressure at 45°C to obtain 2-(7-methoxynaphthalen-1 -yl) ethanamine (oily mass). 10percent Ethyl acetate hydrogenchloride (18.7 ml) was added to a stirred solution of 2-(7-methoxynaphthalen-1 -yl) ethanamine in ethyl acetate (30 ml) at low temperature. The reaction mixture was stirred at room temperature for 2 hr, filtered and evaporated to dryness to obtain 2-(7- methoxynaphthalen-1 -yl) ethanamine hydrochloride (71 gm, 64.28percent yield).
  • 18
  • [ 138113-09-4 ]
  • [ 75-07-0 ]
  • 6-Methoxy-l-methylene-2-acetyl-2-aza-1,2,3,4-tetrahydro-phenanthrene [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; potassium permanganate In tetrahydrofuran; hydrogenchloride; dichloromethane; water 16 6-Methoxy-l-methylene-2-acetyl-2-aza-1,2,3,4-tetrahydro-phenanthrene EXAMPLE 16 6-Methoxy-l-methylene-2-acetyl-2-aza-1,2,3,4-tetrahydro-phenanthrene 2-(7-Methoxynaphth-1-yl)ethylamine (1.35mmol) is dissolved in aqueous hydrochloric acid solution (10 ml 0.1 N HCl). 71 pl of ethanal are then added. The mixture is heated at 70° C. for 3 hours. After cooling, the medium is diluted with 10 ml of water and then washed with ether (10 ml). The aqueous phase is basified by addition of 20 ml of 20% sodium hydroxide, and extracted with dichloromethane. The crude product obtained by evaporation of the. dichloromethane is dissolved in anhydrous THF. To the mixture, cooled to 0° C., is added KMnO4 (3.34 g). portionwise over 35 minutes. The mixture is stirred for 1 h and then filtered. After evaporation of the solvent, 6-methoxy-1-methyl-2-aza-3,4-dihydro-phenanthrene is obtained, which product, on acylation (acetic anhydride, pyridine), leads to 6-methoxy-1-methylene-2-acetyl-2.-aza-1,2,3,4-tetrahydrophenanthrene. Melting, point 171-2° C. NMR: 1 H (CDCl3): 2.24 (St.3H, CH3 CO); 3.19 (t, 2H, CH2 --Ar); 3.92 (s, 3H, OCH3); 4.15 (t, 2H, CH-N); 5.14 and 5.89 (2s, 2H vinylic); 7.17 (d and s, 2H, H-5 and H-7); 7. 60 and 7.51 (2s, 2H, H-9 and H-10) 7.72 (d, 1H, H-8). MS m/z: 267 (M+*), 224, 210, 194, 165, 152.
  • 19
  • [ 138113-09-4 ]
  • [ 59776-88-4 ]
  • [ 138112-81-9 ]
YieldReaction ConditionsOperation in experiment
6 N-[2-(7-methoxynaphth-1-yl)ethyl]-(2-oxopyrrolidin-1-yl)acetamide or 1-{2-[(2-Oxopyrrolidin-1-yl)acetamido]ethyl)-7-Methoxynaphthalene STR13 EXAMPLE 6 N-[2-(7-methoxynaphth-1-yl)ethyl]-(2-oxopyrrolidin-1-yl)acetamide or 1-{2-[(2-Oxopyrrolidin-1-yl)acetamido]ethyl)-7-Methoxynaphthalene STR13 A mixture of 0.02 mol of 2-(7-methoxynaphth-1-yl)ethylamine and 0.022 mol of methyl (-2-oxo-pyrrolidin-1yl)acetate is heated under magnetic agitation at a temperature of 80° C. for 3 hours. The reaction medium is taken up in slightly acid water, and the precipitate formed is spun down and recrystallized in di-n-butyl ether.
  • 20
  • [ 138113-09-4 ]
  • [ 75-36-5 ]
  • [ 138112-76-2 ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine; In dichloromethane; at 0 - 5℃; N-(2-(7-methoxynaphthalen-1-yl)ethyl)acetamide (Agomelatine) 1: A stirred solution of compound 9 (6.5 g, 3.2 mmoles) in dichloromethane (25 mL) was cooled to 0 oC. TEA (5.82 mL, 0.4 mmol) was added to the reaction mixture and followed by addition of acetyl chloride (2.51 mL, 3.5 moles). The resulting reaction mixture was stirred at 0 oC - 5 oC for 30 min. The progress of the reaction was monitored by TLC, after completion of the reaction, the reaction mass was diluted with water (25 mL). Separated the layers and aqueous solution was extracted with dichloromethane (2 x 25 mL) and the combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. The obtained crude compound was triturated with n-Hexane to furnish the 1 (7.37 g, 95%) as an off white solid. (Hexane-EtOAc, 1:1; Rf = 0.7); IR (Neat) cm-1 3252, 2937, 1621, 1509, 1031, 755; mp: 107-108 C (Lit: 107-109 C)4; 1H NMR (400 MHz, DMSO-d6): delta 7.72 (d, J = 8.9 Hz, 1H), 7.64 (dd, J = 6.5, 2.8 Hz, 2H), 7.44 (d, J = 2.4 Hz, 1H), 7.20-7.27 (m, 2 H), 7.13 (dd, J = 2.4, 8.8 Hz, 2H), 5.70 (br s, 1H), 3.95 (s, 3H), 3.58 (q, J = 6.8 Hz, 2H), 3.21 (t, 2H), 1.89 (s, 3 H); 13C NMR (100 MHz, CDCl3): delta 171.30, 158.02, 133.24, 133.12, 130.28, 129.29, 127.15, 123.13, 118.30, 102.35, 55.56, 40.48, 32.96, 22.73. ESI-MS: m/z = 244.1 (M+H, 100%); calcd. for C15H17NO2: 243.0.
92% In pyridine; EXAMPLE 1 N-[2-(7-methoxynaphth-1-yl)ethyl]acetamide 0.01 ml of 2-(7-methoxynaphth-1-yl)ethylamine is dissolved in 6 ml of pyridine. The mixture is cooled in an ice bath with agitation, and 0.012 mol of acetyl chloride is added dropwise. The agitation is maintained for 30 minutes, and then the reaction medium is poured onto ice. The precipitate formed is spun down, washed, dried and recrystallized in isopropyl ether. Yield: 92% Melting point: 109-110 C. Spectral characteristics: Infrared: 3240 cm-1 vNH 1640 cm-1 vCO 1H Nuclear maonetic resonance, solvent CDCl3 delta: 1.93 ppm, singlet, 3H, COCH3 delta: 3.96 ppm, singlet, 3H, OCH3
92% With pyridine; for 0.5h;Cooling with ice;Product distribution / selectivity; 0.01ml of 2-(7-methoxynaphth-l-yl)etylamine is added to 6ml of pyridine. The mixture was cooled in an ice bath with stirring, and 0.012 mol of acetylchloride was added drop wise. The stirring was continued for 30minutes, and then the reaction mass was poured onto ice. The formed precipitate was washed and dried and recrystallized from Isopropyl ether. Yield: 92%
19% With pyridine; In chloroform; at 0 - 20℃; Step 8 N-[2-(7-Methoxy-naphthalen-1-yl)-ethyl]-acetamide: At about 0 C., acetyl chloride (187 mg; 2.4 mmol) was added dropwise to a solution of 2-(7-methoxy-naphthalen-1-yl)-ethylamine (400 mg; 2.0 mmol) in chloroform (15 mL), and pyridine (471 mg; 6.0 mmol). Under continuous stirring, the mixture was maintained at about 0 C. until 2-(7-methoxy-naphthalen-1-yl)-ethylamine was no longer detected by TLC. The mixture was allowed to warm to ambient temperature. The crude product was isolated by standard extractive work up, and purified by flash column chromatography on silica gel (1*16 cm, ethyl acetate/petroleum ether=1:1 elution). Recrystallization from toluene and hexane gave the title product as a white solid (90 mg, 19%). 1H NMR (300 MHz, CDCl3): delta 1.97 (s, 3H), 3.27 (t, J=7.2 Hz, 2H), 3.63 (t, J=6.9 Hz, 2H), 4.04 (s, 3H), 5.59 (br. s, 1H), 7.15 (d, J=8.7 Hz, 1H), 7.27 (s, 2H), 7.47 (s, 1H), 7.68 (d, J=9.0 Hz, 1H), 7.79 (d, J=9.0 Hz, 1H). LC-MS: 244 (M+H)+.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; for 2h; Example 9: Preparation of AgomelatineSolution of acetyl chloride (40 gm) in methylene dichloride (MDC) was added dropwise to a stirred solution of 2-(7-methoxynaphthalen-1 -yl) ethanamine (80 gm), DIPEA (1 08.7 gm) and MDC (400 ml). The reaction mass was stirred for 2 hr at below 0C and quenched with water. The organic layer was separated and washed with water and dried over anhydrous sodium sulphate. The organic layer was dried under reduced pressure. DIPE (240 ml) was added to the reaction mass and stirred for 4 hr at room temperature. The reaction mass was filtered and dried to obtain Agomelatine (68 gm, 82.92% yield).
Reference example 7: The preparation of N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide (agomelatine) 40g 2-(7-methoxy-1-naphthyl)ethylamine was dissolved in 250ml pyridine and heated to 40C for complete dissolution. 21.9g acetyl chloride was slowly added in drops with stirring in ice bath. After completion of addition, the ice bath was removed and the solution was stirred at room temperature for 30min. Subsequently, the reaction solution was poured into 300ml ice water together with vigorous stirring, resulting in a large amount of white precipitate being precipitated. The stirring was carried out for another 1 hour. Then, the solution was filtered and the filter cake was washed by 200ml*2 water to obtain 48g crude product (which was used in the following preparation examples). 1H NMR (400 MHZ, CDCl3): delta 7.77-7.15 (m, 6H, ); delta 5.61 (s, 1H, ); delta 3.99 (s, 3H, ); delta 3.62 (m, 2H, ); delta 3.25 (t, 2H, ); delta 1.95 (s, 3H, ), which is consistent with that in the literature ().

  • 21
  • [ 138113-09-4 ]
  • N-[2-(7-methoxy-1-naphthyl)ethyl]formamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With formic acid 33 N-[2-(7-Methoxynaphth-1-yl)Ethyl]Formamide EXAMPLE 33 N-[2-(7-Methoxynaphth-1-yl)Ethyl]Formamide 0.01 mol of 2-(7-methoxynaphth-1-yl)ethylamine and 0.02 mol of formic acid are placed in a porcelain crucible, and heated at 120° C. until a dry residue is obtained. This is recrystallized. Melting point: 93° C.
  • 22
  • [ 138113-09-4 ]
  • [ 139525-77-2 ]
  • [ 138112-77-3 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 2 N-[2-(7-methoxynaphth-1-yl)ethyl]phenylacetamide 0.01 mol of <strong>[139525-77-2]2-(7-methoxynaphth-1-yl)ethylamine hydrochloride</strong> (obtained by dissolving 2-(7-methoxynaphth-1-yl)ethylamine in ether and bubbling through a current of hydrogen chloride gas, then spinning down the precipitate formed) is dissolved in 60 ml of a water/chloroform mixture.
  • 23
  • [ 1206788-15-9 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; acetic acid In water; isopropyl alcohol at 20 - 80℃; 1.D In a reactor, 1 g of the compound obtained in Step C and 5 eq. of NaBH4 are introduced into a 2-propanol/water 6/1 mixture, and the mixture is stirred at ambient temperature. Acetic acid (0.2 eq.) is then added and the reaction mixture is heated at 80° C. for 8 hours. After evaporating off the solvents and co-evaporation of water with toluene, the crude residue obtained is used directly in the acetylation reaction without further purification.
With hydrazine hydrate In methanol at 30 - 65℃; for 1.16667h; 6 Example 6: Preparation of 1-(2-aminoethyl)-7-methoxynaphthalene (compound of Formula VII): Example 6: Preparation of 1-(2-aminoethyl)-7-methoxynaphthalene (compound of Formula VII): 1-(2-aminoethyl)-7-methoxynaphthalene (compound of Formula VII): 2-(2-(7-methoxynaphthalen-1-yl)ethyl)isoindoline-1,3-dione (15 g) and methanol (150 mL) are charged into a round bottom flask at 30°C. The reaction mass is stirred for 10 minutes at 30°C and hydrazine hydrate (19.4 mL) is added to the reaction mass at the same temperature. The reaction mass is heated to 65°C and maintained for 1 hour at the same temperature. The reaction mass is cooled to 30°C. The reaction mass is filtered and washed with dichloromethane (100 mL). Water (100 mL) is added to the filtrate and extracted with dichloromethane (3 X 100 mL). The layers are separated; the organic layer is washed with brine, and dried over sodium sulphate. The organic layer is evaporated to obtain the title compound as oil.
  • 24
  • [ 138113-09-4 ]
  • [ 108-24-7 ]
  • [ 138112-76-2 ]
YieldReaction ConditionsOperation in experiment
97.5% In tetrahydrofuran; at 0 - 20℃; for 6h; To 500 g of tetrahydrofuran was added 165.7 g (0.82 mol) of 2- (7-methoxy-1-naphthyl) ethylamine, the temperature was lowered to 0 C with stirring, 105.0 g (1.0 mol) of acetic anhydride was slowly added dropwise, After the incubation reaction 3h, the reaction was heated to 20 incubated 3h, the resulting agomelatine reaction solution was washed with water and dried separation, and then concentrated to make, to obtain agomelatine white powder 195.4g (0.80mol) The molar yield was 97.5%.
92% With sodium acetate; In ethanol; at 65℃;Green chemistry; Compound (II) (4.0 g, 16·8 mmol) and sodium acetate (3.0 g, 37.0 mmol) were added to a 100 mL single-mouth flask and dissolved in 40 mL of absolute ethanol to give a suspension liquid; Acetic anhydride (2.0 g, 20.2 mmol) was added with stirring; the reaction was stirred at 65 C., and the reaction was monitored by TLC until the reaction was complete; the reaction solution was poured into saturated aqueous sodium bicarbonate solution to precipitate a large amount of light yellow-brown precipitate; the suspension was filtered by suction. The filter cake was rinsed with water to obtain crude agomelatine crude; the crude agomelatine was dissolved in absolute ethanol/ethyl acetate (nu/nu 7/3), and crystallized after stirring at room temperature; The crystals produced by filtration were dried at 50 C. to give an off-white solid, ie, crystalline form of agomelatine II in an amount of 3.8 g. The yield was 92%. Product properties: white powder. Purity: 99.90 %
90% With triethylamine; In toluene; at 20 - 30℃; Example 8 Synthesis of agomelatine 23.26 g of 2-(7-methoxyl-1-naphthyl) ethylamine prepared in Example 3, 20 ml of triethylamine and 120 ml of toluene into a reaction flask, followed by stirring and then cooling to 20 C; 17 g of acetic anhydride was added dropwise slowly, and the temperature was controlled below 30 C until addition is completed; the reaction was conducted for 4-5 hours at the temperature of 20-30 C, when the reaction was detected to reach completion, 100 ml water was added followed by stirring for 10 minutes and then filtration; the filter cake was rinsed with 3*100 ml of water for 3 times, and the filtrate was allowed for layering, where the toluene layer was extracted for 3 times by adding 3*100 ml of water ; the toluene layer and the filter cake was pooled and concentrated under reduced pressure until dry; 100 ml of toluene was added to the residue, followed by heating to refluxing and maintaining the temperature for 30 minutes; the solution was cooled to 0-5 C to allow for crystallization while stirring for 2 hours, followed by filtration and drying to obtain 25.30 g of white crystalline agomelatine. The yield was 90% and the purity was 99.9%. The HPLC chromatogram was shown in Figure 1. .
83% In toluene; at 40℃; for 3h; 1.6 g of acetic anhydride (15.6 mmols) is added to the toluene solution obtained from example 5 and loaded into a three-necked reaction flask, magnetically stirred and equipped with a temperature probe. The reaction mixture is heated to 40C and maintained at that temperature for about 3 hours. At the end of the reaction, 20 ml of water is added,the phases are separated, and the washing is repeated twice more. The organic phase is evaporated to obtain 2.15 gof Agomelatine. 83% yield from the intermediate 2-(7-methoxynaphthalen-1-yl)ethyl methanesulphonate 25. The productobtained was identified by NMR analysis: 1H NMR (400 MHz, CDCl3) delta 7.78 (m, 1H), 7.71 (m, 1H), 7.49 (m, 1H), 7.30(m, 2H), 7.19 (m, 1H), 5.66 (s, 1H), 4.02 (s, 3H), 3.65 (t, 2H), 3.28 (t, 2H), 1.98 (s, 3H).
83.8% With triethylamine; In toluene; at 0 - 30℃; for 0.5h; To the autoclave was charged 30 g of (7-methoxy-1-naphthyl) acetonitrile prepared in Example 19, 7.5 g of Raney nickel,95% ethanol 200ml, ammonia 60ml, autoclave sealed, nitrogen replacement, access to hydrogen,Control the pressure of 0.3-0.4Mpa, temperature 30-40 , holding pressure after 24 hours, cooling, remove the reaction solution, filter recovery Raney nickel, the filtrate evaporated under vacuum (7-methoxy-1-naphthyl) Ethylamine oil;To the oil was added 120 ml of toluene, 25 ml of triethylamine was stirred and dissolved,Control temperature below 30 add acetic anhydride 17ml, and 0-10 incubation reaction 30min,Then, 120 ml of water was added dropwise and cooled to 0-5 C for 2 h. The mixture was filtered and dried to give 31 g of aggamatine, the yield was 83.8% and the HPLC purity was 99.9%.
80% With sodium acetate; In ethanol;Reflux; In a reactor, 5 g of the compound obtained in Step C and 2 g of sodium acetate are introduced into ethanol. The mixture is stirred, 2.3 g of acetic anhydride are then added, the reaction mixture is heated to reflux and 20 ml of water are added. The reaction mixture is allowed to return to ambient temperature and the precipitate obtained is filtered off, washed with an ethanol/water 35/65 mixture to yield the title product in a yield of 80% with a chemical purity of 99%.Melting point: 108 C.
With sodium acetate; In ethanol;Reflux; In a reactor, 5 g of the compound obtained in Step D and 2 g of sodium acetate are introduced into ethanol. The mixture is stirred, 2.3 g of acetic anhydride are then added, the reaction mixture is heated to reflux and 20 ml of water are added. The reaction mixture is allowed to return to ambient temperature and the precipitate obtained is filtered off and washed with an ethanol/water 35/65 mixture to yield the title product in a yield of 80% for the two Steps D and E and with a chemical purity of more than 99%.Melting point: 108 C.
3 g With sodium acetate; In ethanol; at 30 - 80℃; for 2.4h; Example 11: Preparation of N-[2-(7-methoxy-1-naphthylen-1-yl)ethyl]acetamide (agomelatine):1-(2-aminoethyl)-7-methoxynaphthalene (5.1 g) and ethanol (40 mL) are charged into a round bottom flask at 30C. Sodium acetate (2.51 g) is added to the reaction mass at 30C. Acetic anhydride (3.25 mL) is added to the reaction mass dropwise in 15 minutes at 30C.The reaction mass is heated to 80C and stirred for 2 hours at the same temperature. The reaction mass is cooled to 30C after completion of the reaction and water (250 mL) is added. Dichloromethane (50 mL) is added to the reaction mass and stirred for 15 minutes at 30C. The layers are separated and the aqueous layer is extracted with dichloromethane (50 mL). The combined organic layer is washed with brine solution and dried over sodium sulphate. The solvent from the organic layer is evaporated to obtain a residue. The obtained residue is evaporated with hexane to obtain the product as crude (solid). The crude product is recrystallized in mixture of dichloromethane and hexane. Yield: 3 g.
220 g With triethylamine; In toluene; at 35 - 65℃; for 1.16667h; Example 4 Preparation of the crystalline form VII of agomelatine starting from 2-(7-methoxy-1-naphthyl)methylamine (base) Load 120 g of triethylamine under stirring in a 5 litre reactor containing 210 g of 2-(7-methoxy-1-naphthyl)methylamine (base) in 2500 ml of toluene heated to 35 C. Load 120 g of acetic anhydride in 10 minutes; the temperature will rise to 47 C. Bring to 65 C. and maintain for 1 hour. Stop the heating and load 1000 ml of water, stir for 20 minutes at 50 C., decant for 20 minutes and discard the aqueous phase. Wash the toluene phase at 50 C. with 1000 ml of NaHCO3 2% in water and then with 1000 ml of water. Maintain the toluene phase at 50-60 C. and load it slowly in a reactor pre-cooled to at least -20 C. and containing 400 ml of toluene pre-cooled to -20 C. saturated with agomelatine. Adjust the addition speed so as to maintain the internal temperature always at least -20 C. At the end of the addition leave under stirring for 10-20 minutes and then filter, washing the panel with 400 ml of cold toluene. 220 g wet of agomelatine (polymorph VII) are obtained.

  • 25
  • [ 1207480-89-4 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 2-(7-Methoxy-1-naphthyl)-2-oxoacetamide With aluminum (III) chloride; borane-THF In tetrahydrofuran for 2.5h; Stage #2: With sodium hydroxide In tetrahydrofuran; water 1.C 480 mg of the compound obtained in Step B dissolved in THF (20 ml) are introduced into a reactor, followed by 2 eq. of AlCl3 and finally, slowly, 6 eq. of BH3.THF solution, and the reaction mixture is stirred for 2.5 hours. Water (12 ml) is then added, followed by 25 ml of 1N sodium hydroxide solution together with 800 mg of solid sodium hydroxide, and three extractions with methyl tert-butyl ether (20 ml) are carried out. The solvents are then dried over Na2SO4 and then evaporated off to yield the title product in the form of a yellow oil in a yield of 80% and with a chemical purity of 95%.
  • 26
  • [ 459-72-3 ]
  • [ 138113-09-4 ]
  • 2-fluoro-N-[2-(7-methoxy-naphthalen-1-yl)ethyl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% In 2,2,2-trifluoroethanol for 12h; Reflux; 4.1.2. General protocol for the preparation of compounds 4, 5 General procedure: To a solution of free base of compound A (5.0 mmol) in 10 mL of ethanol trifluoride, was added ethyl 2-fluoroacetate or methyl 2,2-difluoroacetate (15.0 mmol), the reaction mixture was refluxed for 12 h. After concentration under reduced pressure, the obtained residue was poured into 40 mL of water, acidified with an aqueous solution of HCl (3 M) and extracted twice with 50 mL of ethyl acetate. The organic phase was washed with water, dried over MgSO4 and evaporated under reduced pressure to lead to the desired product after recrystallization.
  • 27
  • [ 433-53-4 ]
  • [ 138113-09-4 ]
  • [ 1363155-73-0 ]
YieldReaction ConditionsOperation in experiment
68% In 2,2,2-trifluoroethanol for 12h; Reflux; 4.1.2. General protocol for the preparation of compounds 4, 5 General procedure: To a solution of free base of compound A (5.0 mmol) in 10 mL of ethanol trifluoride, was added ethyl 2-fluoroacetate or methyl 2,2-difluoroacetate (15.0 mmol), the reaction mixture was refluxed for 12 h. After concentration under reduced pressure, the obtained residue was poured into 40 mL of water, acidified with an aqueous solution of HCl (3 M) and extracted twice with 50 mL of ethyl acetate. The organic phase was washed with water, dried over MgSO4 and evaporated under reduced pressure to lead to the desired product after recrystallization.
Reflux;
  • 28
  • [ 6836-21-1 ]
  • [ 138113-09-4 ]
  • 29
  • [ 138113-07-2 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With dimethylsulfide borane complex In toluene at 80 - 85℃; 5 Example 5: Preparation of 2-(7-methoxynaphthalen-1 -yl) ethanamine hydrochloride (formula Vila)Borane-DMS (106 gm) was added to a stirred solution of 2-(7-methoxynaphthalen-1 - yl) acetamide (1 00 gm) and toluene (500 ml) at room temperature. The reaction mixture was heated and maintained at 80-85 °C until reaction completes. The reaction mixture was cooled to room temperature. The reaction mass was slowly quenched into 10% HCI. Solvent was evaporated and Ethyl acetate (50 ml) was added. pH was adjusted to 12 using NaOH solution. The organic layer was separated and washed with water and dried over sodium sulphate. The organic layer was evaporated to dryness under reduced pressure at 45°C to obtain 2-(7-methoxynaphthalen-1 -yl) ethanamine (oily mass). 10% Ethyl acetate hydrogenchloride (18.7 ml) was added to a stirred solution of 2-(7-methoxynaphthalen-1 -yl) ethanamine in ethyl acetate (30 ml) at low temperature. The reaction mixture was stirred at room temperature for 2 hr, filtered and evaporated to dryness to obtain 2-(7- methoxynaphthalen-1 -yl) ethanamine hydrochloride (71 gm, 64.28% yield).
Multi-step reaction with 2 steps 1: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 2: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave
  • 30
  • [ 6836-22-2 ]
  • [ 138113-09-4 ]
  • 31
  • [ 27532-26-9 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: sulfur / ethyl acetate / 10 h / 215 °C 2: sodium hydroxide; water / ethanol / 3 h / 20 °C 3: thionyl chloride / dichloromethane / 2 h / Reflux 4: ammonia / ethyl acetate; water / Cooling with ice 5: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 6: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave
  • 32
  • [ 6836-23-3 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonia / ethyl acetate; water / Cooling with ice 2: triethylamine; trifluoroacetic anhydride / tetrahydrofuran / 20 °C / Cooling with ice 3: hydrogen; ammonia / ethanol; water / 12 h / 60 °C / 228015 Torr / Autoclave
  • 33
  • [ 29921-51-5 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 0.25 h / 20 °C 1.2: 3 h / 20 °C 2.1: n-butyllithium / hexane; tetrahydrofuran / 1.5 h / -78 - 5 °C / Inert atmosphere 2.2: 0.5 h / -78 °C / Inert atmosphere 3.1: ammonium acetate / toluene / 14 h / 100 °C 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 0.25 h / 20 °C 1.2: 3 h / 20 °C 2.1: 1-methyl-pyrrolidin-2-one / 2 h / 150 °C 3.1: diisobutylaluminium hydride / dichloromethane; toluene / 2 h / -78 - 45 °C / Inert atmosphere 4.1: ammonium acetate / toluene / 14 h / 100 °C 5.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
  • 34
  • [ 66240-21-9 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 1.5 h / -78 - 5 °C / Inert atmosphere 1.2: 0.5 h / -78 °C / Inert atmosphere 2.1: ammonium acetate / toluene / 14 h / 100 °C 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
Multi-step reaction with 4 steps 1: 1-methyl-pyrrolidin-2-one / 2 h / 150 °C 2: diisobutylaluminium hydride / dichloromethane; toluene / 2 h / -78 - 45 °C / Inert atmosphere 3: ammonium acetate / toluene / 14 h / 100 °C 4: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
Multi-step reaction with 2 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / ethanol / 2 h / Inert atmosphere; Reflux 2: ammonium hydroxide / dimethyl sulfoxide / 12 h / 150 °C / Autoclave
  • 35
  • [ 158365-54-9 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: diisobutylaluminium hydride / dichloromethane; toluene / 2 h / -78 - 45 °C / Inert atmosphere 2: ammonium acetate / toluene / 14 h / 100 °C 3: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
  • 36
  • [ 158365-55-0 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ammonium acetate / toluene / 14 h / 100 °C 2: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
  • 37
  • [ 1415243-95-6 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
80% With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; 2-(7-Methoxynaphthalen-1-yl)ethanamine 2-(7-Methoxynaphthalen-1-yl)ethanamine (9): A solution of 8 (14 g, 6.1 mmol) and 10% Pd/C (1.4g) in EtOAc (140 mL) was stirred at room temperature under Hydrogen atmosphere (Par shaker at 60 psi) for 8 h. The progress of the reaction was monitored by TLC. After completion of the reaction the catalyst was removed by filtration through celite pad, washed with MeOH (150 mL) and the filtrate was evaporated to dryness under reduced pressure to furnish 9 (9.8 g, 80% yield) as a thick syrup. (Hexane-EtOAc, 1:1 ratio; Rf = 0.4); IR (Neat) cm-1 3357, 2939, 1625, 1260, 1033, 830; 1H NMR (400 MHz, DMSO-d6): δ 7.82 (d, J = 9.2 Hz, 1H), 7.68 (m, 2H), 7.37 (d, J = 2.4 Hz, 1H), 7.27 (m, 2H), 2.87 (t, 2H), 7.17 (dd, J = 8.8 Hz, 2.8 Hz, 1H), 4.14 (m, 1H), 3.90 (s, 3H), 3.08 (t, 2H); 13C NMR (100 MHz, CDCl3): δ 157.71, 134.29, 133.07, 130.33, 129.39, 127.22, 126.74, 123.21, 123.18, 117.91, 117.86, 102.55, 55.35 42.29, 37.19; ESI-MS: m/z = 202.5 (M+H, 100%); calcd. for C13H15NO: 201.2.
  • 38
  • [ 118-46-7 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 5 °C 1.2: 2.5 h / 0 - 5 °C 2.1: potassium carbonate / acetone / 0.25 h / 20 °C 2.2: 3 h / 20 °C 3.1: n-butyllithium / hexane; tetrahydrofuran / 1.5 h / -78 - 5 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere 4.1: ammonium acetate / toluene / 14 h / 100 °C 5.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
Multi-step reaction with 6 steps 1.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 5 °C 1.2: 2.5 h / 0 - 5 °C 2.1: potassium carbonate / acetone / 0.25 h / 20 °C 2.2: 3 h / 20 °C 3.1: 1-methyl-pyrrolidin-2-one / 2 h / 150 °C 4.1: diisobutylaluminium hydride / dichloromethane; toluene / 2 h / -78 - 45 °C / Inert atmosphere 5.1: ammonium acetate / toluene / 14 h / 100 °C 6.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3102.97 Torr
  • 39
  • [ 138113-09-4 ]
  • [ 627-11-2 ]
  • [ 1425498-91-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 20℃;
  • 40
  • [ 138113-09-4 ]
  • N-[2-(7-methoxynaphth-1-yl)ethyl]pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / tetrahydrofuran / Reflux
  • 41
  • [ 138113-09-4 ]
  • [ 1107602-77-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / tetrahydrofuran / 39 h / Reflux
  • 42
  • [ 138113-09-4 ]
  • [ 4635-59-0 ]
  • [ 138112-82-0 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran at 20℃;
  • 43
  • [ 1424944-38-6 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium iodide / N,N-dimethyl-formamide / 2 h / 30 - 102 °C 2: hydrazine hydrate / methanol / 1.17 h / 30 - 65 °C
Multi-step reaction with 3 steps 1.1: potassium carbonate / methanol / 30 °C 1.2: 1.67 h / 30 - 60 °C 2.1: sodium nitrite; 3,5-dihydroxyphenol; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 3 h / 30 - 90 °C 3.1: hydrogen / methanol / 5 h / 30 - 50 °C / Autoclave
  • 44
  • [ 138113-09-4 ]
  • [ 127-09-3 ]
  • [ 138112-76-2 ]
YieldReaction ConditionsOperation in experiment
61% With acetic anhydride In ethanol at 20℃; for 1h; 3 3. Synthesis of Compound 5 Compound 4 (crude product) was dissolved in 150 mL of absolute ethanol and sodium acetate (5.1 g), acetic anhydride, was added(6.3 g) After stirring at room temperature for 1 hour, add water and ethyl acetate, extract, dry, and concentrate to give an oil, which is recrystallized from ethanol:water=5:3 to give 7.3 g of a white solid. Yield 61% (two steps)
  • 45
  • [ 58150-14-4 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium nitrite; 3,5-dihydroxyphenol; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 3 h / 30 - 90 °C 2: hydrogen / methanol / 5 h / 30 - 50 °C / Autoclave
  • 46
  • [ 1424944-40-0 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
0.9 g With hydrogen In methanol at 30 - 50℃; for 5h; Autoclave; 10 Example 10:Example 10: Preparation of 1-(2-aminoethyl)-7-methoxynaphthalene (compound of Formula VII): Example 10:Example 10: Preparation of 1-(2-aminoethyl)-7-methoxynaphthalene (compound of Formula VII): 1-(2-nitroethyl)-7-methoxynaphthalene (1 g) and methanol (40 mL) are charged into an autoclave at 30°C. Raney nickel (1 g) is added to the reaction mass at 30°C. The reaction mass is heated to 50°C and stirred for 5 hours under hydrogen pressure at 50°C. The reaction mass is cooled to 30°C after completion of the reaction. The reaction mass is filtered and washed with methanol (100 mL). The filtrate is concentrated under vacuum to obtain the title compound as residue. Yield: 0.9 g.
  • 47
  • [ 135-19-3 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 2.25 h / 28 - 55 °C 2.1: aluminum (III) chloride / dichloromethane / 0.67 h / 0 °C 2.2: 5.5 h / -10 °C 3.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 3.2: 2 h / 0 - 30 °C 4.1: potassium iodide / N,N-dimethyl-formamide / 2 h / 30 - 102 °C 5.1: hydrazine hydrate / methanol / 1.17 h / 30 - 65 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate / acetone / 2.25 h / 28 - 55 °C 2.1: aluminum (III) chloride / dichloromethane / 0.67 h / 0 °C 2.2: 5.5 h / -10 °C 3.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 3.2: 2 h / 0 - 30 °C 4.1: potassium carbonate / methanol / 30 °C 4.2: 1.67 h / 30 - 60 °C 5.1: sodium nitrite; 3,5-dihydroxyphenol; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 3 h / 30 - 90 °C 6.1: hydrogen / methanol / 5 h / 30 - 50 °C / Autoclave
  • 48
  • [ 1424944-37-5 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 1.2: 2 h / 0 - 30 °C 2.1: potassium iodide / N,N-dimethyl-formamide / 2 h / 30 - 102 °C 3.1: hydrazine hydrate / methanol / 1.17 h / 30 - 65 °C
Multi-step reaction with 4 steps 1.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 1.2: 2 h / 0 - 30 °C 2.1: potassium carbonate / methanol / 30 °C 2.2: 1.67 h / 30 - 60 °C 3.1: sodium nitrite; 3,5-dihydroxyphenol; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 3 h / 30 - 90 °C 4.1: hydrogen / methanol / 5 h / 30 - 50 °C / Autoclave
  • 49
  • [ 1523-11-1 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / dichloromethane / 0.67 h / 0 °C 1.2: 5.5 h / -10 °C 2.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 2.2: 2 h / 0 - 30 °C 3.1: potassium iodide / N,N-dimethyl-formamide / 2 h / 30 - 102 °C 4.1: hydrazine hydrate / methanol / 1.17 h / 30 - 65 °C
Multi-step reaction with 5 steps 1.1: aluminum (III) chloride / dichloromethane / 0.67 h / 0 °C 1.2: 5.5 h / -10 °C 2.1: triethylsilane / dichloromethane / 0.17 h / 30 °C 2.2: 2 h / 0 - 30 °C 3.1: potassium carbonate / methanol / 30 °C 3.2: 1.67 h / 30 - 60 °C 4.1: sodium nitrite; 3,5-dihydroxyphenol; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 3 h / 30 - 90 °C 5.1: hydrogen / methanol / 5 h / 30 - 50 °C / Autoclave
  • 50
  • [ 99416-99-6 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 15 °C 2: dimethyl sulfoxide / 50 °C 3: sodium hydroxide; methanol / 18 h / 40 °C
  • 51
  • [ 185336-04-3 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dimethyl sulfoxide / 50 °C 2: sodium hydroxide; methanol / 18 h / 40 °C
  • 52
  • [ 1424944-39-7 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With methanol; sodium hydroxide at 40℃; for 18h; 5 2-(7-methoxynaphthalen-1-yl)ethanamine 8 The residue obtained from example 4 is dissolved in 15 g of methanol in a three-necked reaction flask, magnetically stirred and equipped with a temperature probe, and 2.24 g of NaOH (56 mmols) is added. The reaction mixtureis heated to 40°C and maintained at that temperature for about 18 hours. At the end of the reaction the solvent is evaporated and 25 ml of water is added. The resulting mixture is extracted three times with 10 ml of toluene each time. The organic phase is washed with 20 ml of water and then dried by azeotropic distillation. A small portion of the solution obtained is concentrated to dryness to identify intermediate 2-(7-methoxynaphthalen-1-yl)ethanamine 8 by NMR analysis: 1H NMR (400 MHz, CDCl3) δ 7.79 (m, 1H), 7.70 (m, 1H), 7.31 (m, 3H), 7.19 (m, 1H), 4.72 (s, 2H), 3.97 (s, 3H), 3.21 (t,2H), 3.14 (t, 2H).
  • 53
  • [ 1123-40-6 ]
  • [ 138113-09-4 ]
  • [ 1595280-06-0 ]
YieldReaction ConditionsOperation in experiment
82% With sodium acetate; acetic acid; for 3h;Reflux; General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol), sodium acetate (82 mg, 1.0 mmol) and cyclic anhydrides 1.0 mmol) in 5mL acetic acid was heated to reflux for 3 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethyl acetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 54
  • [ 1193-54-0 ]
  • [ 138113-09-4 ]
  • [ 1595280-07-1 ]
YieldReaction ConditionsOperation in experiment
70% With sodium acetate; acetic acid; for 3h;Reflux; General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol), sodium acetate (82 mg, 1.0 mmol) and cyclic anhydrides 1.0 mmol) in 5mL acetic acid was heated to reflux for 3 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethyl acetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 55
  • [ 6941-75-9 ]
  • [ 138113-09-4 ]
  • [ 1595280-08-2 ]
YieldReaction ConditionsOperation in experiment
85% With sodium acetate; acetic acid for 3h; Reflux; 1.1.3. General procedure for the synthesis of lactam analogues of Agomelatine (4a-e) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol), sodium acetate (82 mg, 1.0 mmol) and cyclic anhydrides 1.0 mmol) in 5mL acetic acid was heated to reflux for 3 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethyl acetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 56
  • [ 638-32-4 ]
  • [ 138113-09-4 ]
  • [ 1595280-09-3 ]
YieldReaction ConditionsOperation in experiment
79% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 57
  • [ 138113-09-4 ]
  • [ 1595280-15-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 58
  • [ 138113-09-4 ]
  • [ 1595280-16-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 59
  • [ 138113-09-4 ]
  • [ 1595280-17-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 60
  • [ 138113-09-4 ]
  • [ 1595280-18-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 61
  • [ 138113-09-4 ]
  • [ 1595280-19-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 62
  • [ 138113-09-4 ]
  • [ 1595280-20-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 63
  • [ 138113-09-4 ]
  • [ 1595280-21-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetonitrile; N,N-dimethyl-formamide / 2 h / 20 °C 2: triethylamine / 12 h / 20 °C
  • 64
  • [ 2987-87-3 ]
  • [ 138113-09-4 ]
  • [ 1595280-10-6 ]
YieldReaction ConditionsOperation in experiment
74% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 65
  • carboxymethylmethacrylamide [ No CAS ]
  • [ 138113-09-4 ]
  • [ 1595280-11-7 ]
YieldReaction ConditionsOperation in experiment
72% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 66
  • C4H3Cl2NO3 [ No CAS ]
  • [ 138113-09-4 ]
  • [ 1595280-12-8 ]
YieldReaction ConditionsOperation in experiment
68% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 67
  • [ 92116-87-5 ]
  • [ 138113-09-4 ]
  • [ 1595280-13-9 ]
YieldReaction ConditionsOperation in experiment
85% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 68
  • [ 1156216-44-2 ]
  • [ 138113-09-4 ]
  • 2-(1-(2-((2-(7-methoxynaphthalen-1-yl)ethyl)amino)-2-oxoethyl)cyclopentyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In dichloromethane at 20℃; for 6h; 1.1.4. General procedure for the synthesis of acylamino carboxylic acidanalogues of Agomelatine (5a-f) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol) and cyclic anhydrides (1.0 mmol) in 5mL dichloromethane was stirred at room tempreture for 6 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethylacetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 69
  • [ 138113-09-4 ]
  • [ 530-62-1 ]
  • [ 1595280-23-1 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2h; 1.1.5. Generalprocedure for the synthesis of asymmetrical urea analogues of Agomelatine (6a-h) A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 202 mg, 1.0 mmol) and CDI (178 mg, 1.1 mmol) in 20 mL mixed solvent of acetonitrile and N,N-dimethylformamide (4:1) was stirred at room tempreture for 2 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was added to triethylamine (139 μL, 1.0 mmol) and diverse cyclic amines (1.0 mmol) to continue stirred at room tempreture for another 12 h. Then the resulting mixture was concentrated under reduced pressure and 10mL water was added, extracted with ethylacetate (10 mL×3) and the organic layer was washed with 10% hydrochloric acid (10 mL×2), concentrated the organic layer under reduced pressure to obtain pure product.
  • 70
  • [ 17825-86-4 ]
  • [ 138113-09-4 ]
  • [ 1595280-04-8 ]
YieldReaction ConditionsOperation in experiment
73% With sodium acetate; acetic acid for 3h; Reflux; 1.1.3. General procedure for the synthesis of lactam analogues of Agomelatine (4a-e) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol), sodium acetate (82 mg, 1.0 mmol) and cyclic anhydrides 1.0 mmol) in 5mL acetic acid was heated to reflux for 3 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethyl acetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 71
  • [ 123-56-8 ]
  • [ 138113-09-4 ]
  • [ 1595280-05-9 ]
YieldReaction ConditionsOperation in experiment
79% With sodium acetate; acetic acid for 3h; Reflux; 1.1.3. General procedure for the synthesis of lactam analogues of Agomelatine (4a-e) General procedure: A mixture of 2-(7-methoxynaphthalen-1-yl)ethanamine (compound 3, 101 mg, 0.5 mmol), sodium acetate (82 mg, 1.0 mmol) and cyclic anhydrides 1.0 mmol) in 5mL acetic acid was heated to reflux for 3 h in a round bottomed flask. After the completion of reaction (as evidenced by TLC), the resulting mixture was concentrated under reduced pressure and washed with ethyl acetate (10 mL×3), then the concentrated organic layer was purified by column chromatography on silica gel to obtain pure product.
  • 72
  • [ 138113-09-4 ]
  • [ 407-25-0 ]
  • [ 158504-17-7 ]
YieldReaction ConditionsOperation in experiment
79.3% With pyridine for 18h; Reflux; Inert atmosphere;
  • 73
  • [ 116-54-1 ]
  • [ 138113-09-4 ]
  • 2,2-dichloro-N-[2-(7-methoxy-naphthalen-1-yl)ethyl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine Reflux; Inert atmosphere;
  • 74
  • [ 138112-76-2 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
79.5% With sodium dithionite; potassium hydroxide In ethanol; water for 16h; Inert atmosphere; Reflux;
With sodium hydroxide at 100℃;
  • 75
  • 1-cyano-1-(7-methoxyl-1-naphthyl)methyl acetate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
98% With ammonium hydroxide; hydrogen In ethanol at 40 - 50℃; for 7h; Autoclave; 3 Example 3: Use of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl acetate Example 3 Use of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl acetate 30.0 g (0.118 mol) of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl acetate prepared in Example 2, 6 g of Raney nickel, 40 ml of 20% ammonia water and 180 ml of 95% ethanol were charged into an autoclave which is then purged with nitrogen, followed by introducing hydrogen gas; the pressure was controlled at 0.4-0.5 Mpa and the temperature was controlled at 40-50 °C; the reaction was stopped after 7 hours; the reaction solution was cooled to room temperature, then Raney nickel was recovered by filtration; the filtrate was concentrated under reduced pressure until dry; followed by washing once by adding 200 ml of toluene was added, followed by washing once with 100 ml of water; allowing for layering; the toluene layer was washed once by adding 100 ml of saturated brine, followed by layering; the toluene layer was concentrated unde1H-NMR (400 MHz, CDCl3) δ1.80 (s, 3H), 3.05-3.08 (t, J=6.0 Hz, 2H), 3.12-3.16 (t, J=8.0 Hz, 2H), 7.14-7.16 (d, J=8.0 Hz, 1H), 7.22-7.31 (m, 3H), 7.63-7.65 (d, J=8.0 Hz, 1H), 7.72-7.74 (d, J=8.0 Hz, 1H).r reduced pressureto obtain 23.26 g of oily substance 2-(7-methoxyl-1-naphthyl) ethylamine with a yield of 98%.
  • 76
  • 1-cyano-(7-methoxyl-1-naphthyl)methyl propionate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
97% With ammonium hydroxide; hydrogen In ethanol at 50 - 55℃; for 7h; Autoclave; 5 Example 5: Use of 1-cyano-(7-methoxyl-1-naphthyl) methyl propionate Example 5 Use of 1-cyano-(7-methoxyl-1-naphthyl) methyl propionate 31.7 g (0.118 mol) of 1-cyano-(7-methoxyl-1-naphthyl) methyl propionate prepared in Example 4, 6 g of Raney nickel, 40 ml of 20% ammonia water and 180 ml of 95% ethanol were charged into an autoclave which is then purged with nitrogen, followed by introducing hydrogen gas; the pressure was controlled at 0.7-0.8 Mpa and the temperature was controlled at 50-55 °C; the reaction was stopped after 7 hours; the reaction solution was cooled to room temperature, then Raney nickel was recovered by filtration; the filtrate was concentrated under reduced pressure until dry; 200 ml of toluene was added, followed by washing once with 100 ml of water, allowing for layering; the toluene layer was washed once by adding 100 ml of saturated brine, followed by layering; the toluene layer was concentrated under reduced pressure to obtain 22.94 g of oily substance (7-methoxyl-1-naphthyl) ethylamine with a yield of 97%.1H-NMR (400 MHz, CDCl3) δ1.80 (s, 3H), 3.05-3.08 (t, J=6.0 Hz, 2H), 3.12-3.16 (t, J=8.0 Hz, 2H), 7.14-7.16 (d, J=8.0 Hz, 1H), 7.22-7.31 (m, 3H), 7.63-7.65 (d, J=8.0 Hz, 1 H), 7.72-7.74 (d, J=8.0 Hz, 1H).
  • 77
  • 1-cyano-1-(7-methoxyl-1-naphthyl)methyl butyrate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
96% With ammonium hydroxide; hydrogen In ethanol at 40 - 45℃; for 8h; Autoclave; 7 Example 7: Use of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl butyrate Example 7 Use of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl butyrate 33.4 g (0.118 mol) of 1-cyano-1-(7-methoxyl-1-naphthyl) methyl butyrate prepared in Example 6, 6 g of Raney nickel, 40 ml of 20% ammonia water and 180 ml of 95% ethanol were charged into an autoclave which is then purged with nitrogen, followed by introducing hydrogen gas; the pressure was controlled at 0.5-0.6 Mpa and the temperature was controlled at 40-45 °C; the reaction was stopped after 8 hours; the reaction solution was cooled to room temperature, then Raney nickel was recovered by filtration; the filtrate was concentrated under reduced pressure until dry; 200 ml of toluene was added , followed by washing once with 100 ml of water, allowing for layering; the toluene layer was washed once by adding 100 ml of saturated brine, followed by layering; the toluene layer was concentrated under reduced pressure to obtained 22.7 g of oily substance 2-(7-methoxyl-1- naphthyl) ethylamine with a yield of 96%.1H-NMR (400 MHz, CDCl3) δ1.80 (s, 3H), 3.05-3.08 (t, J=6.0 Hz, 2H), 3.12-3.16 (t, J=8.0 Hz, 2H), 7.14-7.16 (d, J=8.0 Hz, 1H), 7.22-7.31 (m, 3H), 7.63-7.65 (d, J=8.0 Hz, 1H), 7.72-7.74 (d, J=8.0 Hz, 1H).
  • 78
  • [ 127299-26-7 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: chloranil / 13 h / Reflux 2: ammonium hydroxide; hydrogen / ethanol / 7 h / 40 - 50 °C / 3000.3 - 3750.38 Torr / Autoclave
Multi-step reaction with 2 steps 1: chloranil / 13 h / Reflux 2: ammonium hydroxide; hydrogen / ethanol / 7 h / 50 - 55 °C / 5250.53 - 6000.6 Torr / Autoclave
Multi-step reaction with 2 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 13 h / Reflux 2: ammonium hydroxide; hydrogen / ethanol / 8 h / 40 - 45 °C / 3750.38 - 4500.45 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 18 h / 30 - 40 °C 2: acetic acid / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 18 h / 30 - 40 °C 2: acetic acid / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 10 - 20 °C 2: acetic acid / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 20 - 30 °C 2: toluene / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 15 h / 10 - 20 °C 2: formic acid / toluene / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 20 h / 30 - 40 °C 2: acetic acid / toluene / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 10 - 20 °C 2: butyric acid / ethyl acetate / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
Multi-step reaction with 3 steps 1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 24 h / 40 - 50 °C 2: acetic acid / toluene / 12 h / Reflux 3: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave

  • 79
  • [ 138112-76-2 ]
  • [ 138113-09-4 ]
  • [ 152302-45-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In water at 100℃;
  • 80
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol formate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: formic acid / toluene / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 81
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol acetate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 82
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol propionate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: toluene / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 83
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol butyrate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: butyric acid / ethyl acetate / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 84
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol isobutyrate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 85
  • 1-cyano-1-(7-methoxy-3,4-dihydro-1-naphthyl)methanol benzoate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / toluene / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 86
  • 1-cyano(7-methoxy-3,4-dihydronaphthalen-1-yl)methyl 4-chlorobenzoate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 87
  • 1-cyano(7-methoxy-3,4-dihydronaphthalen-1-yl)methyl p-nitrobenzoate [ No CAS ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / toluene / 12 h / Reflux 2: ammonia; hydrogen / ethanol / 24 h / 30 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave
  • 88
  • [ 2825-01-6 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-Bromosuccinimide / chloroform / 2 h / 10 °C / Reflux 2: sodium carbonate / toluene / 6 h / 100 °C 3: iron(III) chloride; pyrographite; hydrazine hydrate / methanol / 2 h / 65 °C
  • 89
  • [ 91571-02-7 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / toluene / 6 h / 100 °C 2: iron(III) chloride; pyrographite; hydrazine hydrate / methanol / 2 h / 65 °C
  • 90
  • [ 1424944-40-0 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
96.9% With iron(III) chloride; pyrographite; hydrazine hydrate In methanol at 65℃; for 2h; 1 Example 1 202.2 g (0.87 mol)1- (2-Nitro) ethyl-7-methoxynaphthalene was added to 1000 g of methanol,20.0 g of ferric chloride and 20.0 g of activated carbon were added, heated to 65 ° C,218.0 g mass fraction of 40% hydrazine hydrate (1.74 mol)After the addition was completed, the insulation was refluxed for 2h, cooled to 25 ° C,The resulting 2- (7-methoxy-1-naphthyl) ethylamine reaction mixture,Then filtered and the filtrate evaporated to dryness to give 169.6 g (0.85 mol)2- (7-methoxy-1-naphthyl) ethylamine in a molar yield of 96.9%.
  • 91
  • [ 5302-79-4 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid; sodium nitrite; potassium iodide / acetonitrile / 2 h / 0 - 20 °C 2: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / ethanol / 2 h / Inert atmosphere; Reflux 3: ammonium hydroxide / dimethyl sulfoxide / 12 h / 150 °C / Autoclave
  • 92
  • [ 1095930-99-6 ]
  • [ 138113-09-4 ]
YieldReaction ConditionsOperation in experiment
With ammonium hydroxide In dimethyl sulfoxide at 150℃; for 12h; Autoclave; 2 2. Synthesis of Compound 4 Compound 3 (9.2 g, 50 mmol), DMSO 100 mL, NH3.H2O 120 mL,Placed in a 500 mL autoclave, and reacted at 150° C. for 12 h, cooled to room temperature, diluted with water, extracted with EtOA 2 , dried, and concentrated to give a crude product which was directly used in the next reaction.
  • 93
  • [ 138113-09-4 ]
  • CF3O3S(1-)*C28H20F3O(1+) [ No CAS ]
  • 14-(2-(7-methoxynaphthalen-1-yl)ethyl)-7-(4-(trifluoromethyl)phenyl)-5,6,8,9-tetrahydrodibenzo[c,h]acridin-14-ium trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid; triethylamine In dichloromethane at 20℃; for 4h; Molecular sieve;
Same Skeleton Products
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