* 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 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at 25℃; for 6 h; Inert atmosphere
General procedure: PdCl2(dppf), PdCl2(tbpf) and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66 mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes. Then, PdCl2(dppf) (27.0 mg, 0.033 mmol, 5.0 molpercent), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature under argon for the proper time and then worked up as described above.
65%
at 20℃; for 5 h;
General Procedure 138: 7-Chloroquinoline (Intermediate 573)4,7Dichloroquinoline (10 g, 50 mmol) in THF (100 ml) was degassed with N2 for 5 min. PdCl2dppf (1.2 g, 2 mmol), TMEDA (9.97 g, 86 mmol), and NaBH4 (3.24 g, 86 mmol) were added and the mixture was stirred at room temperature for 5 h. Brine (20 ml) was added dropwise and the solvent was removed in vacuo. The residue dissolved in EtOAc (200 ml), dried (MgSO4) and concentrated in vacuo. The crude residue was purified by column chromatography with heptane/EtOAC (4:1-1:1 gradient) as the eluent to give the title compound (5.4 g, 65percent).MW: 163.61HPLCMS (Method B):[m/z]: 163.90
Reference:
[1] Tetrahedron Letters, 2010, vol. 51, # 12, p. 1562 - 1565
[2] Journal of Molecular Catalysis A: Chemical, 2014, vol. 393, p. 191 - 209
[3] Patent: US2012/214803, 2012, A1, . Location in patent: Page/Page column 185
Reference:
[1] Russian Journal of General Chemistry, 2015, vol. 85, # 12, p. 2725 - 2727[2] Zh. Obshch. Khim., 2015, vol. 85, # 12, p. 1993 - 1995,3
24
[ 108-42-9 ]
[ 56-81-5 ]
[ 612-61-3 ]
[ 635-27-8 ]
Reference:
[1] Journal fuer Praktische Chemie (Leipzig), 1893, vol. <2> 48, p. 263
[2] Journal fuer Praktische Chemie (Leipzig), 1893, vol. <2> 48, p. 283
[3] Chemische Berichte, 1885, vol. 18, p. 2941
[4] Chemische Berichte, 1884, vol. 17, p. 927
[5] Journal of the Chemical Society, 1947, p. 437,44
25
[ 1060737-02-1 ]
[ 612-61-3 ]
[ 14548-50-6 ]
Reference:
[1] Green Chemistry, 2012, vol. 14, # 5, p. 1281 - 1283
26
[ 1375234-69-7 ]
[ 612-61-3 ]
[ 14548-50-6 ]
Reference:
[1] Green Chemistry, 2012, vol. 14, # 5, p. 1281 - 1283
27
[ 6828-35-9 ]
[ 612-61-3 ]
[ 14548-50-6 ]
Reference:
[1] Green Chemistry, 2012, vol. 14, # 5, p. 1281 - 1283
28
[ 612-61-3 ]
[ 90562-35-9 ]
Yield
Reaction Conditions
Operation in experiment
88%
With iron(II) triflate; C13H21N3O2 In chloroform at 40℃; for 4 h; Schlenk technique
General procedure: In a 10 mL Schlenk tube, Fe(OTf)2 (0.005 mmol, 1.8 mg), quinoline (0.5 mmol, 72 mg), Hantzsch ester A(1.25 mmol, 318 mg), and 1.0 mL CHCl3were added. The mixture was stirred at 40oCfor 2 h. The solution was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford the pure 1,2,3,4-tetrahydroquinoline (63.8 mg, 96percent yield).
69%
With hydrogen In acetic acid at 20℃; for 4 h; Under hydrogen
Preparation XLIX 9-Chloro-5,6-dihydro-4H-pyrrolo-[3,2,1-ij]quinoline [0348] 5-Chloro-1,2,3,4-tetrahydroquinoline [0349] A mixture of 5-chloroquinoline (10.0 g) and platinum oxide (50 mg) in acetic acid was shaken under a hydrogen atmosphere at room temperature for 4 hours. The mixture was diluted with diethyl ether and filtered through Celite. The volatiles were removed under reduced pressure and the residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate (3.x.300 mL). The organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified over silica gel and the fractions containing product were combined and concentrated under reduced pressure to provide 7.0 g (69percent) of the desired compound. [0350] MS (EI m/z) C9H10ClN (M+1) [0351] Ring Formation/Decarboxylation [0352] Beginning with 5-chloro-1,2,3,4-tetrahydroquinoline, the title compound was prepared essentially as described in Preparation I. [0353] MS (EI m/z) C11H10ClN (M+) 192.1 [0354] Analysis for C11H10ClN: [TABLE-US-00002] Calcd: C, 68.93; H 5.25; N, 7.30; Found: C, 69.18; H, 5.25; N, 6.97.
Reference:
[1] Journal of the American Chemical Society, 2018, vol. 140, # 12, p. 4417 - 4429
[2] Tetrahedron Letters, 2017, vol. 58, # 36, p. 3571 - 3573
[3] Patent: US2003/229026, 2003, A1, . Location in patent: Page 25
With iron(II) triflate; C13H21N3O2; In chloroform; at 40℃; for 4.0h;Schlenk technique;
General procedure: In a 10 mL Schlenk tube, Fe(OTf)2 (0.005 mmol, 1.8 mg), quinoline (0.5 mmol, 72 mg), Hantzsch ester A(1.25 mmol, 318 mg), and 1.0 mL CHCl3were added. The mixture was stirred at 40oCfor 2 h. The solution was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford the pure 1,2,3,4-tetrahydroquinoline (63.8 mg, 96% yield).
69%
With hydrogen;platinum(IV) oxide; In acetic acid; at 20℃; for 4.0h;Under hydrogen;
Preparation XLIX 9-Chloro-5,6-dihydro-4H-pyrrolo-[3,2,1-ij]quinoline [0348] 5-Chloro-1,2,3,4-tetrahydroquinoline [0349] A mixture of 5-chloroquinoline (10.0 g) and platinum oxide (50 mg) in acetic acid was shaken under a hydrogen atmosphere at room temperature for 4 hours. The mixture was diluted with diethyl ether and filtered through Celite. The volatiles were removed under reduced pressure and the residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate (3×300 mL). The organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified over silica gel and the fractions containing product were combined and concentrated under reduced pressure to provide 7.0 g (69%) of the desired compound. [0350] MS (EI m/z) C9H10ClN (M+1) [0351] Ring Formation/Decarboxylation [0352] Beginning with 5-chloro-1,2,3,4-tetrahydroquinoline, the title compound was prepared essentially as described in Preparation I. [0353] MS (EI m/z) C11H10ClN (M+) 192.1 [0354] Analysis for C11H10ClN: [TABLE-US-00002] Calcd: C, 68.93; H 5.25; N, 7.30; Found: C, 69.18; H, 5.25; N, 6.97.
Example 6 3- (7-chloro-4-quinolinvl)-2-methvl-lHp, vrrolof2, 3-blpyridine-1-acetic acid, sodium salt a) 7-chloro-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-quinoline 2-methyl-1H-pyrrolo [2, 3-b]pyridine (0.4g), 4-chloroquinoline (0.6g) and N methyl pyrrolidine (lml) were stirred at 100C over 2 days. The reaction mixture was triturated with diethyl ether and filtered to give a solid, which was further purified by silica chromatography eluting with ethhyl acetate: isoheaxane (3: 7) to give the sub-title compound (31mg). MS ES+ 293 [M+1]
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine; In tetrahydrofuran; at 25℃; for 6h;Inert atmosphere;
General procedure: PdCl2(dppf), PdCl2(tbpf) and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66 mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes. Then, PdCl2(dppf) (27.0 mg, 0.033 mmol, 5.0 mol%), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature under argon for the proper time and then worked up as described above.
65%
With sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; at 20℃; for 5h;
General Procedure 138: 7-Chloroquinoline (Intermediate 573)4,7Dichloroquinoline (10 g, 50 mmol) in THF (100 ml) was degassed with N2 for 5 min. PdCl2dppf (1.2 g, 2 mmol), TMEDA (9.97 g, 86 mmol), and NaBH4 (3.24 g, 86 mmol) were added and the mixture was stirred at room temperature for 5 h. Brine (20 ml) was added dropwise and the solvent was removed in vacuo. The residue dissolved in EtOAc (200 ml), dried (MgSO4) and concentrated in vacuo. The crude residue was purified by column chromatography with heptane/EtOAC (4:1-1:1 gradient) as the eluent to give the title compound (5.4 g, 65%).MW: 163.61HPLCMS (Method B):[m/z]: 163.90
With tetrachloromethane; iron(III) chloride hexahydrate; at 150℃; for 8h;Inert atmosphere; Sealed tube;
General procedure: An ampule was charged with 0.02 mmol of FeCl3·6H2O, 2 mmol of aniline, 4 mmol of carbon tetrachloride, and 8 mmol 1,3-propanediol under argon. The sealed ampule was placed into a pressure reactor, which was hermetically closed and heated at 150C for 8 h with continuous stirring. After the reaction completion, the reactor was cooled to room temperature, the ampule was opened, the reaction mixture was poured in hydrochloric acid. The aqueous layer was separated, neutralized with 10% sodium hydroxide solution, and extracted with methylenechloride. The organic layer was filtered, the solvent was distilled off, and the residue was distilled in a vacuum. Physicochemical characteristics and spectral data of the obtained compounds 2a-2l corresponded to the literature data.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 12h;
General procedure: To a solution of the corresponding N-heterocycles (10.0 mmol) in CH2Cl2 (20 mL), m-chloroperoxybenzoic acid (m-CPBA, 20.0 mmol, 2.0 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 12 h. Then saturated aqueous NaHCO3 (20 mL) was added. The aqueous was extracted with CH2Cl2 (10 mL x 3) and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EtOAc/n-hexene or EtOAc/MeOH to afford desired N-oxides.
methyl 3-(2-acetamido-7-chloroquinolin-1(2H)-yl)acrylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With tetra-n-butylphosphonium acetate; In tetrahydrofuran; at 25℃; for 12h;
General procedure: To a stirred solution of amide (1.5 mmol), propiolate (1.0mmol), and TBPA (20 mol%) in THF (3 mL), the N-heterocycle(1.0 mmol) was added slowly at 25 C (for 10 min), and theresulting mixture was stirred at ambient temperature for 12 h.After completion of the reaction (monitored by TLC), themixture was evaporated in vacuo followed by addition of H2O(10 mL), and the pH was adjusted to 2 using concentrated HCl.Afterwards, CH2Cl2 (5 mL) was added, the mixture was stirredfor an additional 30 min, and two layers were separated. Theaqueous layer was extracted with CH2Cl2 (3 × 10 mL), the combinedorganic layers were dried over MgSO4, filtered, and concentratedin vacuo to yield the crude product (purity 75-82%).