* 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.
A mixture of compound 14 (3.0 g, 16 mmol), 10 percent Pd-C (0.7 g) and ethanol (20 ml) was heated in an autoclave at 100°C under 50 atmospheres of H2 for 15 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give a crude solid. This was purified by recrystallization from MeOH to give compound 15 (1.8 g, 9.4 mmol, 53percent) as a colorless crystal. 1H-NMR (270 MHz) δ (CDCl3) 6.96-6.68 (m, 3H), 3.79 (s, 3H), 3.33 (s, 3H), 2.95-2.56 (m, 4H) ppm.
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 7, p. 1017 - 1024
[2] Patent: EP1175417, 2004, B1, . Location in patent: Page 14
[3] Patent: US6180647, 2001, B2,
2
[ 1416897-52-3 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 1, p. 468 - 473
3
[ 5263-87-6 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 7, p. 1017 - 1024
4
[ 21979-59-9 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 7, p. 1017 - 1024
5
[ 5961-59-1 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 1, p. 468 - 473
6
[ 940-11-4 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 1, p. 468 - 473
With hydrogen;palladium 10% on activated carbon; In ethanol; at 100.0℃; under 38002.6 Torr; for 15.0h;
A mixture of compound 14 (3.0 g, 16 mmol), 10 % Pd-C (0.7 g) and ethanol (20 ml) was heated in an autoclave at 100C under 50 atmospheres of H2 for 15 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give a crude solid. This was purified by recrystallization from MeOH to give compound 15 (1.8 g, 9.4 mmol, 53%) as a colorless crystal. 1H-NMR (270 MHz) delta (CDCl3) 6.96-6.68 (m, 3H), 3.79 (s, 3H), 3.33 (s, 3H), 2.95-2.56 (m, 4H) ppm.
Pd-C; In H2; ethanol;
(ii) 6-Methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline (Compound 15) A mixture of compound 14 (3.0 g, 16 mmol), 10% Pd-C (0.7 g) and EtOH (20 ml) was heated in an autoclave at 100 C. under 50 atm of H2 for 15hr. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give a crude solid. This was purified by recrystallization from MeOH to give compound 15 (1.8 g, 9.4 mmol, 53%) as a colorless crystal. 1H-NMR (270 MHz) delta (CDCl3) 6.96-6.68 (m, 3H), 3.79 (s, 3H), 3.33 (s, 3H), 2.95-2.56 (m, 4H) ppm.
With Lawessons reagent; In toluene; for 1.5h;Heating / reflux;
To a stirred solution of compound 15 (350 mg, 1.83 mmol) in toluene (5 ml) was added Lawesson's Reagent (407 mg, 1.01 mmol), and refluxed for 1.5 hours. The solvent was evaporated, and the residue was purified by a column chromatography on silica gel to give compound 46 (363 mg, 1.75 mmol, 96%) as a white solid. 1H-NMR (270MHz) delta (CDCl3) 7.06 (1H, d, J = 8.8 Hz), 6.79 (1H, dd, J = 8.8, 2.9 Hz), 6.72 (1H, d, J = 2.9 Hz), 3.89 (3H, s), 3.81 (3H, s), 3.21 - 3.14 (2H, m), 2.81 - 2.74 (2H, m) ppm.
(i) 6-Hydroxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline (Compound 22) To a stirred solution of compound 15 (500 mg, 2.61 mmol) in CH2Cl2 (7 ml) was added BBr3 (1.0M in CH2Cl2, 5.74 ml, 5.74 mmol) at room temperature, and stirred for 3h. The mixture was poured into ice water. The aqueous layer was extracted with AcOEt (*2). The combined organic layers were washed with sat. NaCl aq, dried (MgSO4), filtered, and concentrated to give compound 22 (350 mg, 76%) as a colorless crystal. 1H-NMR (270 MHz) delta (CDCl3) 6.85 (1H, d, J=8.4 Hz), 6.75-6.70 (m, 2H), 3.34 (3H, s), 2.86 (2H, t, J=7.1 Hz), 2.63 (2H, t, J=7.1 Hz) ppm.
76%
With boron tribromide; In dichloromethane; at 20.0℃; for 3.0h;
To a stirred solution of compound 15 (500 mg, 2.61mmol) in CH2Cl2 (7 ml) was added BBr3 (1.0 M in CH2Cl2, 5.74 ml, 5.74 mmol) at room temperature, and stirred for 3h. The mixture was poured into ice water. The aqueous layer was extracted with ethyl acetate (x 2). The combined organic layers were washed with sat. NaCl aq, dried (MgSO4), filtered, and concentrated to give compound 22 (350 mg, 76%) as a colorless crystal. 1H-NMR (270MHz) delta (CDCl3) 6.85 (1H, d, J = 8.4 Hz), 6.75-6.70 (m, 2H), 3.34 (3H, s), 2.86 (2H, t, J = 7.1 Hz), 2.63 (2H, t, J = 7.1 Hz) ppm.
With potassium hexamethylsilazane; In tetrahydrofuran; toluene;
PREPARATION 25 6-Methoxy-1,3,3-trimethyl-3,4-dihydro-1H-quinolin-2-one To 6-Methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one (1.00 g, 5.23 mmol) in 30 mL of THF at room temperature was added KHMDS (0.5 M in toluene; 22.0 mL, 10.9 mmol). After 15 minutes, methyl iodide (1.55 g, 10.9 mmol) was added and the reaction was stirred overnight. The KHMDS/Mel addition was repeated in the morning, and after stirring for several hours the mixture was quenched with water and extracted twice with ethyl acetate. The extracts were washed successively with water and brine, dried over sodium sulfate and concentrated. Silica gel chromatography (3:1 hexanes/EtOAc) gave 356 mg (31%) of the title compound as a yellow oil.
With iodine; silver trifluoroacetate; In dichloromethane;
PREPARATION 40 7-Iodo-<strong>[187679-62-5]6-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one</strong> Silver trifluoroacetate (2.32 g, 10.48 mmol) was added to a dry methylene chloride (100 ml) solution of 6-Methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one (1.0 g, 5.24 mmol) followed by the dropwise addition of methylene chloride (100 ml) solution of iodine (1.33 g, 10.48 mmol) over 15 minutes. The reaction mixture was stirred overnight and the precipitated silver iodide salts were filtered off. The filtrate was concentrated down to a residue which was chromatographed using 50% ethylacetate/hexane to yield the title compound (795 mg, 48% yield). 1H NMR (400 MHz, CDCl3) delta2.57-2.61 (2H, m), 2.81-2.85 (2H, m), 3.27 (3H, s), 3.82 (3H, s), 6.62 (1H, s), 7.31 (1H, s). m/z (APCI+) 318 (M+1). HPLC (aqueous 200 Mm ammonium acetate buffer/acetonitrile gradient, 3.0 ml/min, Hewlett Packard ODS Hypersil 5 muM, 125*4 mm column), 4.959 min.
PREPARATION 34 6-Hydroxy-1-methyl-3,4-dihydro-1H-quinolin-2-one 5.74 ml of 1.0 M BBr3/CH2Cl2 solution was added to a dry CH2Cl2 solution of <strong>[187679-62-5]6-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one</strong> (500 mg, 2.62 mmol) under nitrogen. The reaction mixture was stirred for 2 hours, poured into ice water and extracted with ethyl acetate (150 ml). The combined organic extract was washed with brine,dried (MgSO4) and the solvent was evaporated under reduced pressure to yield the title compound as a pink solid (392 mg, 84%). 1H NMR (400 MHz, CD3OD) delta2.52-2.56 (2H, m), 2.77-2.81 (2H, m), 3.28 (3H,s), 6.62-6.67 (2H, m), 6.92 (1H, d, J=8.72 Hz). m/z (APCI-) 176 (M-1). HPLC (aqueous 200 Mm ammonium acetate buffer/acetonitrile gradient, 3.0 ml/min, Hewlett Packard ODS Hypersil 5 muM, 125*4 mm column), 2.51 minutes.
of(2S,3S)-3-[(6-Methoxy-1-methyl-2-thioxo-1,2,3,4-tetrahydroquinolin-7-yl)methyl]amino-2-phenylpiperidinedihydrochloride[ No CAS ]
[ 187679-81-8 ]
Yield
Reaction Conditions
Operation in experiment
96%
In toluene;
(i) 6-Methoxy-1-methyl-2-thioxo-1,2,3,4-tetrahydroquinoline (Compound 46) To a stirred solution of compound 15 (350 mg, 1.83 mmol) in toluene (5 ml) was added Lawesson's Reagent (407 mg, 1.01 mmol), and refluxed for 1.5 h. The solvent was evaporated, and the residue was purified by a column chromatography on silicagel to give compound 46 (363 mg, 1.75 mmol, 96%) as a white solid. 1H-NMR (270 MHz) delta (CDCl3) 7.06 (1H, d, J=8.8 Hz), 6.79 (1H dd, J=8.8, 2.9 Hz), 6.72 (1H, d, J=2.9 Hz), 3.89 (3H, s), 3.81 (3H, s), 3.21-3.14 (2H, m), 2.81-2.74 (2H, m) ppm.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
