* 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.
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 12 h;
6-chloroquinoline (0.3 mmol, 49 mg)Tetrahydroxy diboron (0.9mmol, 81mg),Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile,40 ° C for 12 hours,The residue was purified by thin layer chromatography to give 47.6 mg of 6-chloro tetrahydroquinoline in 95percent yield, 98percent purity,
84%
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 8 h; Schlenk technique
General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg,0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg,1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 °C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98percent yield).
83%
With palladium; hydrogen In acetonitrile at 30℃; for 16 h;
To a solution of PdNPore (2.7 mg, 5 molpercent) in acetonitrile (5 mL) was added the substrate 6-chloroquinoline(81.8 mg, 0.5 mmol), hydrogen (5 bar), placed on a magnetic stirrer at 30 ° C for 16 h, column chromatography (silica gel, 200-300Methyl acetate) to give 6-chloro-1,2,3,4-tetrahydroquinoline 69.57 mg in 83percent yield,
79%
With ethanol; Dimethylphenylsilane; Au-TiO2 In neat (no solvent) at 70℃; for 3 h;
General procedure: To a dry vial containing 8-methoxyquinoline, 1 (0.048 g, 0.3 mmol), Me2PhSiH (185 μL, 1.2mmol) and ethanol (70 μL, 1.2 mmol), Au/TiO2 (60 mg, 1.0 molpercent) was added. The Au contentin catalyst was ~1 wtpercent. The mixture was heated to 70 oC and the progress of reaction wasmonitored by TLC and GC. After 15 min (100percent conversion), ethanol (1 mL) was added and theresulting slurry was filtered under reduced pressure through a short pad of silica gel with the aidof ethanol (2-3 mL) to withhold the supported catalyst. The filtrate was evaporated undervacuum and the residue was chromatographed (n-hexane/ethyl acetate, 10:1) to afford 8-methoxy-1,2,3,4-tetrahydroquinoline (1a) (41 mg, 84percent yield).
78%
Stage #1: With hydrogenchloride; hydrogen In ethanol; water at 20℃; Stage #2: With sodium hydrogencarbonate In water
To a solution of 6-chloroquinoline (1.5 g, 9.17 mmol) in C2H5OH (50 ml) was added Pt02 (41.5 mg, 0.18 mmol) and concentrated HC1 (0.1 ml) under an atmosphere of hydrogen gas. The reaction was stirred overnight at room temperature, then concentrated in vacuo, diluted with water (100 ml), adjusted to pH 8 with aqueous sodium bicarbonate. The resulting solution was extracted with dichloromethane (3 x 80 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate, concentrated in vacuo to afford 6-chloro-l,2,3,4- tetrahydroquinoline as a colorless oil (1.2 g, 78 ).LC/MS (ES, m/z) [M+H]+ 168.0'H-NMR (300 MHz, CDCI3) δ 6.90 - 6.98 (m, 2H), 6.39 - 6.42 (t, / = 1.2 Hz, 1H), 3.23 - 3.35 (m, 2H), 2.73 - 2.81 (m, 2H), 1.91 - 1.96 (m, 2H)
62%
With hydrogen In methanol for 4 h;
A flask filled with a mixture of 6-chloroquinoline (12.0 g, 73.3 mmol), PtO2 (2.16 g, 13 mol percent), and MeOH (500 mL, 6.15 M) was flushed with N2 and then equipped with a balloon filled with H2. The reaction was kept under H2 atmosphere and stirred for 4 h. The mixture was filtered through Celite and washed with CH2Cl2. Purification via silica gel chromatography using 50percent CH2Cl2 in hexanes gave 6-chloro-1,2,3,4-tetrahydroquinoline (7.7 g, 62percent). 1H NMR (400 MHz, DMSO-d6) δ 6.85-6.83 (m, 2H), 6.42-6.39 (m, 1H), 5.82 (s, 1H), 3.17-3.13 (m, 2H), 2.64 (t, J=6.3 Hz, 2H), 1.78-1.72 (m, 2H). LC/MS (10percent-99percent CH3CN (0.035percent TFA)/H2O (0.05percent TFA)), m/z: M+1 obs=168.2; tR=1.57 min.
Reference：
[1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 17, p. 7956 - 7967
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 50, p. 15656 - 15661[3] Angew. Chem., 2016, vol. 128, # 50, p. 15885 - 15890,6
[4] Organic Letters, 2013, vol. 15, # 7, p. 1484 - 1487
[5] Chemical Communications, 2013, vol. 49, # 63, p. 7052 - 7054
[6] Patent: CN106831565, 2017, A, . Location in patent: Paragraph 0103; 0104; 0105; 0106
[7] Tetrahedron Letters, 1987, vol. 28, # 1, p. 77 - 80
[8] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 9, p. 2968 - 2976
[9] Angewandte Chemie - International Edition, 2017, vol. 56, # 12, p. 3216 - 3220[10] Angew. Chem., 2017, vol. 129, # 12, p. 3264 - 3268,5
[11] Advanced Synthesis and Catalysis, 2015, vol. 357, # 16-17, p. 3529 - 3537
[12] Angewandte Chemie - International Edition, 2018, vol. 57, # 35, p. 11262 - 11266[13] Angew. Chem., 2018, vol. 130, # 35, p. 11432 - 11436,5
[14] Catalysis Science and Technology, 2017, vol. 7, # 10, p. 1981 - 1985
[15] Advanced Synthesis and Catalysis, 2015, vol. 357, # 4, p. 753 - 760
[16] Tetrahedron, 2018, vol. 74, # 17, p. 2121 - 2129
[17] Patent: CN106432072, 2017, A, . Location in patent: Paragraph 0056-0063
[18] Journal of the American Chemical Society, 2015, vol. 137, # 36, p. 11718 - 11724
[19] Arkivoc, 2015, vol. 2015, # 3, p. 38 - 51
[20] Patent: WO2012/94462, 2012, A2, . Location in patent: Page/Page column 72
[21] Journal of the American Chemical Society, 2018, vol. 140, # 1, p. 433 - 440
[22] Patent: US2008/27067, 2008, A1, . Location in patent: Page/Page column 264
[23] Catalysis Science and Technology, 2018, vol. 8, # 10, p. 2648 - 2653
[24] Synlett, 1998, # 9, p. 1029 - 1030
[25] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 9, p. 955 - 977
[26] Chemische Berichte, 1922, vol. 55, p. 3780
[27] Chemische Berichte, 1913, vol. 46, p. 3182
[28] Helvetica Chimica Acta, 1985, vol. 68, p. 1952 - 1960
[29] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17592 - 17598,7
[30] ACS Catalysis, 2016, vol. 6, # 9, p. 5816 - 5822
[31] Green Chemistry, 2017, vol. 19, # 3, p. 749 - 756
[32] Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9419 - 9422
[33] ACS Catalysis, 2018, vol. 8, # 1, p. 17 - 21
[34] Tetrahedron Letters, 2018, vol. 59, # 10, p. 949 - 953
[35] Organic Letters, 2018, vol. 20, # 4, p. 1171 - 1174
[36] Applied Catalysis A: General, 2018, vol. 560, p. 37 - 41
[37] Angewandte Chemie - International Edition, 2018, vol. 57, # 31, p. 9950 - 9954[38] Angew. Chem., 2018, vol. 130, p. 10098 - 10102,5
2
[ 612-57-7 ]
[ 635-46-1 ]
[ 49716-18-9 ]
Reference：
[1] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17592 - 17598,7
[2] Molecular Catalysis, 2018, vol. 452, p. 145 - 153
Reference：
[1] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17592 - 17598,7
[2] Journal of Materials Chemistry A, 2017, vol. 5, # 7, p. 3260 - 3266
Reference：
[1] Journal of the American Chemical Society, 1952, vol. 74, p. 3176
[2] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 12, p. 3639 - 3648
8
[ 17049-49-9 ]
[ 49716-18-9 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 9, p. 1255 - 1258
9
[ 635-46-1 ]
[ 49716-18-9 ]
[ 90562-36-0 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 17, p. 5119 - 5123
10
[ 106-47-8 ]
[ 49716-18-9 ]
Reference：
[1] Chemische Berichte, 1913, vol. 46, p. 3182
11
[ 635-46-1 ]
[ 49716-18-9 ]
[ 90562-36-0 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 17, p. 5119 - 5123
With tetrahydroxydiboron; copper diacetate; In acetonitrile; at 40℃; for 12h;
<strong>[612-57-7]6-chloroquinoline</strong> (0.3 mmol, 49 mg)Tetrahydroxy diboron (0.9mmol, 81mg),Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile,40 C for 12 hours,The residue was purified by thin layer chromatography to give 47.6 mg of 6-chloro tetrahydroquinoline in 95% yield, 98% purity,
84%
With tetrahydroxydiboron; copper diacetate; In acetonitrile; at 40℃; for 8h;Schlenk technique;
General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg,0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg,1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98% yield).
83%
With palladium; hydrogen; In acetonitrile; at 30℃; under 3750.38 Torr; for 16h;Catalytic behavior;
To a solution of PdNPore (2.7 mg, 5 mol%) in acetonitrile (5 mL) was added the substrate <strong>[612-57-7]6-chloroquinoline</strong>(81.8 mg, 0.5 mmol), hydrogen (5 bar), placed on a magnetic stirrer at 30 C for 16 h, column chromatography (silica gel, 200-300Methyl acetate) to give 6-chloro-1,2,3,4-tetrahydroquinoline 69.57 mg in 83% yield,
79%
With ethanol; Dimethylphenylsilane; Au-TiO2; In neat (no solvent); at 70℃; for 3h;
General procedure: To a dry vial containing 8-methoxyquinoline, 1 (0.048 g, 0.3 mmol), Me2PhSiH (185 muL, 1.2mmol) and ethanol (70 muL, 1.2 mmol), Au/TiO2 (60 mg, 1.0 mol%) was added. The Au contentin catalyst was ~1 wt%. The mixture was heated to 70 oC and the progress of reaction wasmonitored by TLC and GC. After 15 min (100% conversion), ethanol (1 mL) was added and theresulting slurry was filtered under reduced pressure through a short pad of silica gel with the aidof ethanol (2-3 mL) to withhold the supported catalyst. The filtrate was evaporated undervacuum and the residue was chromatographed (n-hexane/ethyl acetate, 10:1) to afford 8-methoxy-1,2,3,4-tetrahydroquinoline (1a) (41 mg, 84% yield).
78%
To a solution of <strong>[612-57-7]6-chloroquinoline</strong> (1.5 g, 9.17 mmol) in C2H5OH (50 ml) was added Pt02 (41.5 mg, 0.18 mmol) and concentrated HC1 (0.1 ml) under an atmosphere of hydrogen gas. The reaction was stirred overnight at room temperature, then concentrated in vacuo, diluted with water (100 ml), adjusted to pH 8 with aqueous sodium bicarbonate. The resulting solution was extracted with dichloromethane (3 x 80 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate, concentrated in vacuo to afford 6-chloro-l,2,3,4- tetrahydroquinoline as a colorless oil (1.2 g, 78 ).LC/MS (ES, m/z) [M+H]+ 168.0'H-NMR (300 MHz, CDCI3) delta 6.90 - 6.98 (m, 2H), 6.39 - 6.42 (t, / = 1.2 Hz, 1H), 3.23 - 3.35 (m, 2H), 2.73 - 2.81 (m, 2H), 1.91 - 1.96 (m, 2H)
62%
With hydrogen;platinum(IV) oxide; In methanol; for 4h;
A flask filled with a mixture of <strong>[612-57-7]6-chloroquinoline</strong> (12.0 g, 73.3 mmol), PtO2 (2.16 g, 13 mol %), and MeOH (500 mL, 6.15 M) was flushed with N2 and then equipped with a balloon filled with H2. The reaction was kept under H2 atmosphere and stirred for 4 h. The mixture was filtered through Celite and washed with CH2Cl2. Purification via silica gel chromatography using 50% CH2Cl2 in hexanes gave 6-chloro-1,2,3,4-tetrahydroquinoline (7.7 g, 62%). 1H NMR (400 MHz, DMSO-d6) delta 6.85-6.83 (m, 2H), 6.42-6.39 (m, 1H), 5.82 (s, 1H), 3.17-3.13 (m, 2H), 2.64 (t, J=6.3 Hz, 2H), 1.78-1.72 (m, 2H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=168.2; tR=1.57 min.
With hydrogen; In pentan-1-ol; water; at 130℃; under 22502.3 Torr; for 2.5h;Autoclave;Catalytic behavior;
General procedure: In a typical experiment, the above-prepared thermoregulated phasetransferPt nanocatalyst, n-decane (100 mg) and a certain amount ofsubstrates were added in the autoclave. Then the reactor was replacedthree times with 2 MPa H2 and stirred under hydrogen pressure at adesignated temperature for an appointed time. After reaction, the reactorwas cooled to room temperature and depressurized. The upperproduct phase was easily separated from the lower catalyst phase anddirectly analysed by GC and GC-MS.
77%Chromat.
With Co3CuO(x); hydrogen; In tetrahydrofuran; at 80℃; under 7500.75 - 30003 Torr; for 15h;Autoclave; Sealed tube;
General procedure: The hydrogenation reactions of quinolines were carried out in16 mL stainless steel autoclaves with a Teflon inner container in a batch mode of operation [33,34]. In a typical reaction, quinoline (0.129 g,1 mmol), catalyst 20 mg and THF (1 mL) were added into the inner container, which was transferred into the autoclave. The reactor was sealed and charged with 1 MPa of H2 to remove the air for three times. After that, it was charged with 4 MPa of H2 and heated to 60 C andstirred for 15 h. Upon completion of reaction, the solid catalyst was separated using an extra magnet, and the liquid was analysed on a gas chromatograph (GC9720, Zhejiang Fuli Analytical Instruments Co.,Ltd., China) equipped with a flame ionization detector and a HP-5 capillary column (30m×0.32mm×0.25 mum) with toluene as an internal standard and GC-MS (Agilent 6890N-5975) with a HP-5 capillarycolumn (30m×0.32mm×0.25 mum).
With C16H26MnN3O3P(1+)*Br(1-); potassium tert-butylate; hydrogen; In tetrahydrofuran; at 120℃; under 60006 Torr; for 16h;Autoclave;
General procedure: In a glove box filled with argon, potassium tert-butoxide (5.6 mg, 0.05 mmol), and a manganese catalyst (0.005 mmol) were sequentially added to a 4 mL glass bottle with a stirrer, the manganese catalysts being Formula I to Formula IV, respectively. The manganese catalysts of the structure shown are recorded as manganese catalysts [Mn] -1, [Mn] -2, [Mn] -3, [Mn] -4), tetrahydrofuran (0.5 mL) and quinoline (0.25 mmol), Cap the bottle cap, insert a needle with a vent hole (length 3cm, hole diameter 1mm) into the bottle cap, put the glass bottle into the autoclave, and then remove the autoclave from the glove box. Replace the argon gas in the autoclave with hydrogen (3 × 10bar), then fill with 80bar hydrogen, and react at 120 C for 16h. After the reaction, the ice-water bath is cooled, and the gas in the autoclave is carefully released. The resulting reaction product system is sampled for The target product was obtained by GC quantification and separation by column chromatography.
With 2,6-dimethylpyridine; In 1,2-dichloro-ethane; at 70℃;
Under an N2 atmosphere at RT, ethyl-O-trifluoromethylsulfonyl-L-lactate (1.2 mL, 6.56 mmol) was slowly added to a stirring solution of <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> (1.0 g, 5.97 mmol) and 2,6-lutidine (0.8 mL, 6.87 mmol) in 1,2-dichloroethane (15 mL), and the reaction was heated at 70 C. overnight. The mixture was washed with H2O and extracted twice with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in hexanes gave (R)-ethyl 2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)propanoate as a yellow oil (1.54 g, 96%). 1H NMR (300 MHz, CDCl3): delta 6.9 (m, 2H), 6.46 (d, 1H), 4.4 (q, 1H), 4.16 (m, 2H), 3.29 (m, 2H), 2.71 (m, 2H), 1.93 (m, 2H), 1.49 (d, 3H), 1.22 (t, 3H).
With 2,6-dimethylpyridine; In 1,2-dichloro-ethane; at 25 - 70℃; for 19h;
(R)-1-(Methoxycarbonyl)-2-methylpropyl-trifluoromethane sulfonate (200 mg, 0.75 mmol) in 1,2-dichloroethane (1 mL), was slowly added to a stirring solution of <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> (100 mg, 0.60 mmol), 2,6-lutidine (0.105 mL, 9.09 mmol), and 1,2-dichloroethane (5 mL), under N2, at 25 C. The reaction was heated at 70 C. for 19 hours. The mixture was washed with H2O and extracted twice with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in hexanes gave the desired ester as a yellow oil (30 mg, 0.11 mmol, 15% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA), m/z: M+1 obs=282.2; tR=4.04 min.
REFERENCE EXAMPLE 22 4.9 g of ethyl ethoxymethylenemalonate was added to 4 g of <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> and the mixture was heated on an oil bath at 110 C. during which time distillation of ethanol was observed. After heating the mixture at the same temperature as above for 30 minutes, 30 g of polyphosphoric acid was added thereto followed by heating at 140 C. for 30 minutes. After completion of the reaction, the reaction mixture was poured into 200 ml of water and the resulting mixture was rendered neutral with a 40% aqueous sodium hydroxide solution to precipitate light brown crystals. Without further purification, the crystals were mixed with 100 ml of a 10% aqueous sodium hydroxide solution and the mixture was heat-refluxed for 40 minutes during which time the crystals were dissolved to form a uniform solution. The solution was treated with activated carbon while hot and filtered. The filtrate was allowed to cool and adjusted pH value to pH 2 to obtain 7.0 g of 9-chloro-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid as light yellow crystals having a melting point of 282 to 286 C.
Example 3; (S)-methyl 4-(3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-2-oxopyrrolidin-1-yl)phenylsulfonylcarbamate; Step 1: (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one; Under an N2 atmosphere at -20 C., N,N-diisopropylethylamine (1.74 mL, 10 mmol) was added dropwise to a solution of (R)-(+)(alpha-hydroxy-gamma-butyrolactone (0.39 mL, 5 mmol) in dichloromethane (8 mL). Then trifluoromethanesulfonic anhydride (0.88 mL, 5.25 mmol) was added dropwise by maintaining internal temperature of the reaction mixture <-20 C. Upon completion of addition, the mixture was stirred at -20 C. for 1 hour. Then at -20 C., 6-Cl tetrahydroquinolin (1.26 g, 7.5 mmol) was added dropwise. The reaction was allowed to warm to RT over a period of 30 minutes and continued to stir at RT for 16 h. The reaction mixture was diluted with 200 mL of ethylacetate and washed with saturated sodium bicarbonate (3×). The organic layer was washed with a saturated aqueous NaCl solution (2×). The solution was dried over magnesium sulfate, filtered, and concentrated. Purification of the residue by silica gel chromatography using 10-30% ethyl acetate in hexane gave (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one (1.14 g) as white solid. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=252.2; tR=3.20 min.
(S)-N-allyl-6-(3-(6-chloro-3,4-dihydroquinolin-l(2H)-yl)-2-oxopyrrolidin-l-yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide. Prepared using General Procedure 4, Method A. To a stirring solution of (R)-N-allyl-6-(3-hydroxyl-2-oxopyrrolidin- 1 -yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide (75 mg, 0.20 mmol) in DCM (0.6 mL), under N2, was added diisopropylethylamine (70 muL, 0.40 mmol). The solution was then cooled to - 40 0C in a dry ice/acetone bath and triflic anhydride was added (37 muL, 0.22 mmol). The reaction was stirred at - 40 0C for 30 minutes then a solution of 6-chloro- 1,2,3,4-tetrahydroquino line (50 mg, 0.30 mmol) dissolved in DCM (0.3 mL) was added. The solution was allowed to warm to - 20 0C and was placed in the - 20 0C freezer overnight. The solution was then allowed to warm to room temperature and was washed with saturated aqueous NaHCO3 (5 mL), and the aqueous layer extracted once with DCM (5 mL). The organic layers were combined and concentrated. The residue was purified by silica gel chromatography with 5%-70% EtOAc in hexanes to give (S)-N-allyl-6-(3-(6- chloro-3 ,4-dihydroquinolin-1(2H)-yl)- 2-oxopyrrolidin-1 -yl)-N-(thiazol-2-yl)pyridine-3- sulfonamide (94 mg) in 89% yield. LC/MS (10%-99% CH3CN/eta2O (0.05% TFA)), m/z: M+l obs = 530.1, tR= 2.05 min.
6-chloro-N-[E-1-hydroxyadamantan-4-yl]-3,4-dihydroquinoline-1(2H)-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of E-4-aminoadamantan-1-ol obtained in Reference Example 2 (225 mg) in a mixture of chloroform (5 ml) and N,N-dimethylformamide (3 ml), N,N'-carbonyldiimidazole (241 mg) was added and stirred at room temperature for 1 hour. To the reaction mixture, a solution of triethylamine (0.23 ml) and <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> (260 mg) in chloroform (3 ml) was then added and the resulting mixture was heated to reflux and stirred for 8 hours. After cooling at room temperature, the reaction mixture was diluted with ethyl acetate and washed sequentially with 1.2M hydrochloric acid and brine. The organic layer was dried over anhydrous magnesium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluding solvent: chloroform:methanol = 19:1) to give the titled compound (170 mg) as a light-yellow powder. 1H NMR (300 MHz, CHLOROFORM-D) delta 1.36-1.63 (m, 4 H), 1.67-1.81 (m, 4 H), 1.83-2.00 (m, 4 H), 2.04-2.23 (m, 3 H), 2.74 (t, J=6.7 Hz, 2 H), 3.68-3.78 (m, 2 H), 3.88-4.07 (m, 1 H), 5.26 (d, J=6.37 Hz, 1 H), 7.10-7.21 (m, 2 H), 7.24-7.35 (m, 1 H).
To a solution of methyl 3-chloro-2-oxo-l,2-dihydroquinoxaline-6-carboxylate (1.0 g, 4.19 mmo in NMP (10.0 ml) was added 6-chloro-l ,2,3,4-tetrahydroquinoline (1.20 g, 7.16 mmol) and the reaction was stirred for 1 h at 150C in an oil bath. The reaction mixture was cooled down to room temperature, precipitated with water (100 ml). The solids were collected by filtration and dried in an oven under reduced pressure to afford methyl 3-(6-chloro-l,2,3,4-tetrahydroquinolin l-yl)-2-oxo-l ,2-dihydroquinoxaline-6-carboxylate as a gray solid (1.0 g, crude).LC/MS (ES, m/z): [M+H]+ 370.0
With hydrogen; In methanol; at 80℃; under 750.075 Torr; for 4h;Autoclave;
General procedure: Typically, 1.0 mmol of quinoline compounds, 6 mL of solvent and acertain amount of PdCIL-T catalyst were added into a 50 mL PTFEreaction vessel or thick walled pressure vessel. The mixture was stirredfor 2 min to ensure complete dispersion of the catalyst and then placedin a 50 mL stainless-steel autoclave. After being flushed three timeswith H2, the pressure was elevated to 1-10 atm at room temperature.The autoclave was then heated to 30-120 C with a magnetic stir for acertain time. Subsequently, the catalyst was removed from the mixtureby centrifugation, and the liquid sample was analyzed by GC or GC-MS.The calculations of conversion and selectivity were based on the followingformula: Conversion=[consumed substrate]/[initial substrate]×100%, Selectivity=[py-THQs]/[all hydrogenated products]×100%.
Carbon material preparation As described in Example 1,To a Schlenk flask was added 0.5 mmol of 6-chloro-1,2,3,4-tetrahydroquinoline,20 mg of catalyst,Oxygen balloon as oxygen source,The reaction was stirred at 100 C for 12 h,Get the corresponding target product,The yield was 85%.
71%
With oxygen; iron(II) chloride; In para-xylene; dimethyl sulfoxide; at 110℃; for 28h;Schlenk technique;
General procedure: To a Schlenk tube equipped with a magnetic stir bar were added8-methyl-1,2,3,4-tetrohydroquinoline (0.50 mmol), FeCl2 (1.9mg, 1.5·10-2 mmol), DMSO (31.2 mg, 0.4 mmol), and p-xylene (1mL). The reaction mixture was stirred at 110 C under anoxygen atmosphere using a balloon and monitored by TLC. Afterthe reaction, the mixture was cooled to room temperature andpurified using flash chromatography (hexane-EtOAc, 10:1) togive the corresponding product 8-methylquinoline in 70% yield.8-MethylquinolineColorless oil. 1H NMR (400 MHz, CDCl3): delta = 8.93 (m, 1 H), 8.10(m, 1 H), 7.64 (d, J = 4.0 Hz, 1 H), 7.54 (m, 1 H), 7.43-7.35 (m, 2H) 2.82 (s, 3 H). 13C NMR (100 MHz, CDCl3): delta = 149.2, 147.3,137.1, 136.3, 129.6, 128.3, 126.3, 125.9, 120.8, 18.2. HRMS: m/zcalcd for [C10H9N + H+]: 144.0813; found: 144.0813.
59%
With cobalt(II) 5,10,15,20-tetraphenylporphyrin; oxygen; In N,N-dimethyl-formamide; for 12h;
General procedure: N-Heterocyclic amine (0.50 mmol), CoTPP (10 mg) and DMF (2 mL) were mixed in a carousel reaction tube. The reaction mixture was stirred at 120 C under oxygen atmosphere, the reaction was sampled periodically and monitored by TLC (petroleum ether/ethyl acetate (10:1 v/v)). After the reaction, the reaction mixture was then cooled to room temperature and purified using flash chromatography to give the corresponding product. All the dehydrogenation products are known, and their NMR spectra were consistent with the literature. NMR spectra were recorded at 25 C on an Bruker AVANCE III 400-NMR spectrometer at 400 MHz for 1H and 100 MHz for 13C, using CDCl3 as solvent with TMS as the internal standard. Thin-layer chromatography was performed on silica gel 60 F254 (Sinopharm) thin-layer chromatography plates using petroleum ether/ethyl acetate (10:1 v/v) as the mobile phase.
With oxygen; In 1,3,5-trimethyl-benzene; at 80℃; under 760.051 Torr; for 8h;
General procedure: 200mg Ni2Mn-LDH type hydrotalcite catalyst, 0.5mmol tetrahydroquinoline and 2mL 1,3,5-trimethylbenzene solvent Was added to the reactor, the reaction was carried out at atmospheric pressure and at a temperature of 80 C. The reaction time was 2.5 h under an atmosphere of oxygen, and the contents of the quinoline, the starting material, in the liquid were analyzed by gas chromatography internal standard method (nitrobenzene as internal standard) Content,The conversion and selectivity of the reaction were calculated. The conversion of tetrahydroquinoline was> 99% and the selectivity of the reaction was 78.3%
tert-butyl (6-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)hexyl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With sodium tris(acetoxy)borohydride; In 1,2-dichloro-ethane; at 20℃;
Sodium triacetoxyborohydride (1.67 g, 7.9 mmol) was added in one portion to a stirred solution of <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> (0.662 g, 3.95 mmol) and 21 (1.7 g, 7.9 mmol) in 1 ,2-dichloroethane (20 mL). The resulting reaction mixture was stirred at room temperature overnight. Saturated aqueous NaHCO3 was added to the reaction mixture and it was extracted with chloroform. The organic phase was washed with brine, dried over anhydrous Na2504, filtered and concentrated under reduced pressure. Purification by silica gel flash chromatography, eluting with hexanes, then hexanes/ethyl acetate, from 95/5 to 85/15, afforded 0.95 g (2.6 mmol, 66% yield) of pure, target product, as a colorless oil. ?H NMR (400 MHz, CDC13): = 9.98-6.96 (dd, 1 H); 6.90-6.89 (d, 1 H); 6.46-6.44 (d, 1 H); 4.55 (bs, 1 H); 3.27-3.24 (t, 2 H); 3.22-3.19 (t, 2 H); 3.15-3.10 (m, 2 H); 2.73-2.70 (t, 2 H);1.96-1.90 (m, 2 H); 1.61-1.55 (m, 2 H); 1.53-1.46 (m + s, 2 + 9 H); 1.41-1.35 (m, 4 H).
With triethylamine; In dichloromethane; at 0 - 25℃;
[00156] Acid chloride obtained from Step 1, was taken up in dichioromethane (20 mL) and a solution of 2 (11.5 mmols, 1.9 g, 0.9 eq) and triethyl amine (38.2 mmols, 3.86 g, 3.0 eq) in dichloromethane (10 mL) was added dropwise at 0 C. The reaction was stirred at 25 C for 30 mm. The reaction progress was monitored by TLC. It was then diluted with dichloromethane, and washed successively with saturation solution ammonium chloride, saturation solution sodium bicarbonate and brine. The crude product was purified by silica gel chromatography (Petroleum ether/ethyl acetate, 4/1) to give the desired product 14 (2.00 g, 6.53 mmols, 5 1.3%) as a white solid.
2-(chloromethyl)-3-methyl-7-(propan-2-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one[ No CAS ]
2-[(6-chloro-3,4-dihydroquinolin-1(2H)-yl)methyl]-3-methyl-7-(propan-2-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
27%
With caesium carbonate; In acetonitrile; at 80℃; for 12h;
A mixture of 2-(chloromethyl)-3-methyl-7-(propan-2-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one (96 mg, 0.4 mmol), Cs2CO3(260 mg, 0.8 mmol) and <strong>[49716-18-9]6-chloro-1,2,3,4-tetrahydroquinoline</strong> (134 mg, 0.8 mmol) in MeCN (3 mL) was heated at 80C over 12 h. The precipitate was filtered and the filtrate was purified by preparative HPLC (MeCN and H2O with 0.05% NH3.H2O as mobile phase) to give the titled compound (40 mg, yield 27%).1H-NMR (400 MHz, CDCl3): delta 1.30 (d, J = 6.8 Hz, 6H), 2.03-2.06 (m, 2H), 2.80-2.84 (m, 2H), 3.37-3.41 (m, 3H), 3.54 (s, 3H), 4.49 (s, 2H), 6.50-6.52 (m, 1H), 6.98-7.03 (m, 2H), 7.85 (s, 1H).
methyl 4-((6-chloro-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With sodium tris(acetoxy)borohydride; In 1,2-dichloro-ethane; at 20℃;
NaBH(OAc)3 (552 mg, 2.60 mmol) was added in one portion to a stirred solution of 6- chloro- l,2,3,4-tetrahydroquinoline (400 mg, 2.39 mmol) and methyl 4-formylbenzoate (356 mg, 2.17 mmol) in anhydrous DCE (11 mL). The resulting reaction mixture was stirred at room temperature overnight, under an argon atmosphere. TLC after this time, eluting with hexanes/EtOAc, 6/4, showed almost complete consumption of the starting material. The reaction was stopped. Saturated aqueous NaHC03 was added to the reaction mixture and it was extracted with chloroform. The organic phase was washed with brine, dried over anhydrous Na2S04, filtered and concentrated under vacuum. The crude product was recrystallized from methanol to afford the desired product as a white powder (480 mg, 70%). 1H NMR (400 MHz, CDC13) delta 8.00 (d, / = 8.4 Hz), 7.31 (d, = 8 Hz, 2H), 6.97 (d, = 2.4 Hz, 1H), 6.90 (dd, J = 8.8, 2.4 Hz, 1 H), 6.33 (d, J = 8.8 Hz, 1 H), 4.51 (s, 2H), 3.93 (s, 3H), 3.39 (t, = 5.6 Hz, 2H), 2.82 (t, = 6.4 Hz, 2H), 2.07 - 2.01 (m, 2H).13C NMR (100 MHz, CDC13) delta 166.9, 144.0, 143.8, 130.0 (2C), 129.0, 128.7, 126.8, 126.4 (2C), 124.0, 120.7, 112.0, 55.3, 52.0, 50.0, 28.0, 22.1.
With triethylamine; In acetonitrile; at 130℃; for 0.5h;Sealed tube;
General procedure: To a microwave vial was added 30 mg of the sulfonyl chloride,1.5 eq. of the appropriate amine, 1.2 eq. of triethylamine, and 300 muL ofacetonitrile. The vial was sealed and heated at 130 C for 30 min. Themixture was diluted with dichloromethane and the organic phase waswashed 2 times with water and brine. The organic layer was dried overNa2SO4 and concentrated in vacuo. Crude sulfonamide products werepurified either by recrystallization from ethanol or by flash chromatography0-75% EtOAc/Hexanes.
With oxygen; benzoic acid; cobalt(II) chloride; In 1,4-dioxane; at 80℃; for 7h;
0.8 mmol of <strong>[49716-18-9]6-chlorotetrahydroquinolin</strong>e, 0.5 mmol of indole, <strong>[49716-18-9]6-chlorotetrahydroquinolin</strong>e, 10% by mass of cobalt chloride,<strong>[49716-18-9]6-chlorotetrahydroquinolin</strong>e 80% benzoic acid and 2.0 ml of 1,4-dioxane, stirred at 80 C for 7 hours under oxygen conditions, cooled to room temperature after completion of the reaction, diluted reaction solution, filtered The filtrate was taken, and the solvent was evaporated under reduced pressure to give a crude material. The crude product was purified by column chromatography to afford product 6a as a yellow solid, yield 76%, purity 97%.
With hydrogen; In neat (no solvent); at 100℃; under 3750.38 Torr; for 2h;Autoclave; Sealed tube;
General procedure: All organic compounds (Tokyo Chemical Industry, Japan) were usedwithout further purification. Hydrogenation reactions were carried outin 10 mL autoclave with a glass tube inside equipped with magneticstirrer. In a typical experiment, 1 mmol of substrate and catalyst (1 mol%) were placed in the reactor and sealed. After being sealed, hydrogenwas introduced to reactor and inside of the reactor was purged formultiple times. The reactor was pressurized at 5-10 bar by hydrogen and heated to 100 C-180 C. After completion of reaction, the reactorwas cooled to room temperature and depressurized. The obtained re-action crude washed with acetone several times and resultant solutionwas filtered by using micro filters (Sartorius RC 0.20 mum). Then, thefiltrate solution was concentrated by using rotary evaporation.Conversion and yield of product were obtained by 1 H NMR analysisusing 1, 3, 5-trimethoxybenzene as an internal standard. 1 H NMRspectra were recorded using Brucker UltraShield 400 plus operating at400 MHz.
With hydrogen; In water; at 100℃; under 15001.5 Torr; for 4h;Autoclave;
General procedure: The quinoline hydrogenation was tested in a stainless steelautoclave under magnetic stirring. In a typical run, 3.0mLof water, 60 L of quinoline and 0.1g of Au catalysts wereadded to the autoclave. After sealing, nitrogen was introducedto remove air for several times and pressurized withH2of 2.0MPa. And then the reactor was heated to 100Cand remained at this temperature under stirring. The reactionmixture was cooled and then extracted with ethyl acetatefor 3 times when the reaction was completed. The resultantextract was measured by gas chromatography/massspectrometry.
With sodium tris(acetoxy)borohydride; glacial acetic acid In dichloromethane at 25℃; for 12h;
42a.1; 42b.1 Step 1: cis- and trans-tert-butyl (3-(6-chloro-3,4-dihydroquinolin-l(2H )-yl)cyclobutyl)carbamate
To a solution of 6-chloro-l,2,3,4-tetrahydroquinoline (500 mg, 2.98 mmol) in dichloromethane (20 mL) were added tert-butyl N-(3-oxocyclobutyl)carbamate (1.1 g, 5.97 mmol), sodium triacetoxyborohydride (1.9 g, 8.95 mmol) and acetic acid (179 mg, 2.98 mmol). After stirring at 25 °C for 12 h, the mixture was filtered and concentrated under reduced pressure. The residue was purified by RP- HPLC to the title compound as a mixture of both cis and trans isomers. LCMS RT = 2.152 min, m/z = 337.3 [M+H]+.
With sodium tris(acetoxy)borohydride; glacial acetic acid In dichloromethane at 25℃; for 12h;
42a.1; 42b.1 Step 1: cis- and trans-tert-butyl (3-(6-chloro-3,4-dihydroquinolin-l(2H )-yl)cyclobutyl)carbamate
To a solution of 6-chloro-l,2,3,4-tetrahydroquinoline (500 mg, 2.98 mmol) in dichloromethane (20 mL) were added tert-butyl N-(3-oxocyclobutyl)carbamate (1.1 g, 5.97 mmol), sodium triacetoxyborohydride (1.9 g, 8.95 mmol) and acetic acid (179 mg, 2.98 mmol). After stirring at 25 °C for 12 h, the mixture was filtered and concentrated under reduced pressure. The residue was purified by RP- HPLC to the title compound as a mixture of both cis and trans isomers. LCMS RT = 2.152 min, m/z = 337.3 [M+H]+.
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