* 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 sodium tetrahydroborate In tetrahydrofuran at 20 - 35℃; for 0.5 h;
Methyl quinoline 2-carboxylate 2 (5 g, 26.8 mmol) in solution in THF (30 mL) was added, at room temperature, to a solution of NaBH4 (710 mg, 18.8 mmol) in THF (20 mL). The mixture was stirred at 35 °C for 30 min. Then, at 35 °C, methanol (2.5 mL) was added followed by warm water (30 mL), and finally ethyl acetate (20mL). The organic layer was washed with water (2×30 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude yellow-blue residue was purified through a silica gel column chromatography (AcOEt/MCH: 60/40). White solid; 73percent yield; mp 135 °C (dec); 1H NMR (300 MHz, CDCl3) 4.68 (1H, s, OH), 4.95 (2H, s, CH2), 7.31 (1H, m, CHar), 7.55 (1H, m, CHar), 7.71 (1H, m, CHar), 7.81 (1H, m, CHar), 8.10 (2H, m, CHar); 13C NMR (75 MHz, CDCl3) 64.25, 118.43, 126.35, 127.55, 127.69, 128.57, 129.81, 136.86, 146.72, 159.19; Anal. Calcd. for C10H9NO C, 75.45; H, 5.70; N, 8.80. Found C, 75.13; H, 5.56; N, 8.75.
Reference：
[1] Organic Letters, 2005, vol. 7, # 17, p. 3609 - 3612
[2] Tetrahedron Letters, 2012, vol. 53, # 35, p. 4747 - 4750
[3] Tetrahedron, 2013, vol. 69, # 44, p. 9322 - 9328
[4] Tetrahedron Asymmetry, 2009, vol. 20, # 14, p. 1672 - 1682
[5] Journal of Organic Chemistry, 1953, vol. 18, p. 55,56
2
[ 5470-96-2 ]
[ 1780-17-2 ]
Yield
Reaction Conditions
Operation in experiment
85%
Stage #1: With sodium tetrahydroborate In methanol for 0.333333 h; Stage #2: With water In methanol
Example 16 2-(2,6-Dioxo-piperidin-3-yl)-4-(quinolin-2-ylmethoxy)-isoindole-l,3-dioneStep 1 :[207] 2-Quinolinecarbaldehyde (2.00 g, 12.7 mmol) was dissolved in 25 mL of methanol. To this solution was added sodium borohydride (0.24 g, 6.4 mmol) in small portions over a period of 20 minutes. Then 2 mL of water were added and the mixture was evaporated. The residue was dissolved in ethyl acetate (75 mL) and washed with water (3 x 75 mL) and evaporated. The residue was chromatographed in CH2Cl2-methanol gradient, eluting the product at 97:3 CH2Cl2-methanol, and providing 1.7 g of quinolin-2-yl-methanol in 85percent yield; 1H NMR (CDCl3) δ 4.92 (s, 2H), 7.26 (d, J = 2.1 Hz, IH), 7.30-7.57 (m, IH), <n="68"/>7.68-7.75 (m, IH), 7.82 (dd, J = 8.0 Hz, J = 0.9 Hz, IH), 8.07 (d, J = 8.4 Hz, IH), 8.13 (d, J = 8.5 Hz, IH).
Reference：
[1] Tetrahedron, 1999, vol. 55, # 41, p. 12069 - 12078
[2] Tetrahedron Letters, 2013, vol. 54, # 38, p. 5211 - 5213
[3] Chemistry - An Asian Journal, 2017, vol. 12, # 2, p. 239 - 247
[4] Patent: WO2008/115516, 2008, A2, . Location in patent: Page/Page column 66-67
[5] ChemCatChem, 2015, vol. 7, # 8, p. 1292 - 1301
[6] Archiv der Pharmazie (Weinheim, Germany), 1959, vol. 292, p. 682,690
[7] Archiv der Pharmazie (Weinheim, Germany), 1959, vol. 292, p. 682,690
[8] Patent: US2003/229026, 2003, A1, . Location in patent: Page 27-28
[9] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4364 - 4374
[10] Patent: US9321730, 2016, B2, . Location in patent: Page/Page column 14
3
[ 60483-07-0 ]
[ 1780-17-2 ]
Reference：
[1] Yakugaku Zasshi, 1954, vol. 74, p. 790[2] Chem.Abstr., 1955, p. 11646
[3] Journal of the American Chemical Society, 1954, vol. 76, p. 1286,1289
[4] Patent: EP1228067, 2004, B1, . Location in patent: Page 67
4
[ 61831-29-6 ]
[ 1780-17-2 ]
Reference：
[1] Synlett, 2008, # 4, p. 543 - 546
[2] Chemische Berichte, 1936, vol. 69, p. 534
5
[ 1076-28-4 ]
[ 1780-17-2 ]
Reference：
[1] Journal of Organometallic Chemistry, 2008, vol. 693, # 18, p. 3063 - 3073
[2] Chemische Berichte, 1936, vol. 69, p. 534
[3] Yakugaku Zasshi, 1958, vol. 78, p. 608,610[4] Chem.Abstr., 1958, p. 18420
6
[ 91-63-4 ]
[ 1780-17-2 ]
Reference：
[1] Journal of the American Chemical Society, 1954, vol. 76, p. 1286,1289
[2] Tetrahedron Letters, 2013, vol. 54, # 38, p. 5211 - 5213
[3] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4364 - 4374
7
[ 63430-96-6 ]
[ 1780-17-2 ]
Reference：
[1] Angewandte Chemie - International Edition, 2013, vol. 52, # 27, p. 6983 - 6987[2] Ross. Khim. Zh., 2013, vol. 125, # 27, p. 7121 - 7125,5
Reference：
[1] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
[2] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
Reference：
[1] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
[2] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
Reference：
[1] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
[2] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1430 - 1440
16
[ 4491-33-2 ]
[ 1780-17-2 ]
Reference：
[1] Chemische Berichte, 1952, vol. 85, p. 152,158
Reference：
[1] Yakugaku Zasshi, 1954, vol. 74, p. 790[2] Chem.Abstr., 1955, p. 11646
26
[ 1780-17-2 ]
[ 5632-15-5 ]
Yield
Reaction Conditions
Operation in experiment
83%
With phosphorus tribromide In dichloromethane at 0 - 20℃;
Quinolin-2-ylmethanol 7 (6 g, 37.8 mmol) was dissolved in CH2Cl2 (60 mL). PBr3 (2.14 mL, 22.6 mmol) was carefully added at 0 °C to this solution. The mixture was allowed to return at ambient temperature and was stirred for 30 min. Water (60 mL) was then added followed by a saturated aqueous solution of K2CO3 (40 mL) to obtain a pH=8. The organic phase was washed with brine (2×30 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The crude residue was purified through a silica gel column chromatography (AcOEt/MCH: 20/80). White solid; 83percent yield; mp 55 °C (dec); 1H NMR (300 MHz, DMSO) 4.86 (2H, s, CH2), 7.67 (2H, m, CHar), 7.78 (1H, m, CHar), 7.99 (2H, m, CHar), 8.40 (1H, m, CHar); 13C NMR (75 MHz, DMSO) 35.67, 122.10, 127.46, 127.54, 128.34, 129.07, 130.53, 138.37, 147.36, 157.67; HRMS (ESI) m/z calculated for C10H9NBr [M+H]+: 221.99129, found: 221.991.
68%
With dibromo sulfoxide In toluene at 110℃; for 1 h;
PREPARATION 302-(Bromomethyl)quinolineThe title compound of Preparation 29 (3.68 g, 23.1 mmol) was suspended in 60 ml toluene. Thionyl bromide (12.0 g, 57.8 mmol) was slowly added and the mixture was heated at 110°C for 1 h. The mixture was concentrated under reduced pressure and the residue was partitioned between water and dichloromethane. The aqueous phase was basified with potassium carbonate and extracted three times with dichloromethane. The combined organics were washed with water, brine and dried over sodium sulphate and evaporated. The residue was purified by column chromatography (ethyl acetate-hexane, 5:95) to give 3.5 g (15.8 mmol, 68percent) of the title compound as a solid. Purity 100percent.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.72 (s, 2 H), 7.54 - 7.62 (m, 2H), 7.70 - 7.79 (m, 1 H), 7.83 (d, J=8.21 Hz, 1 H), 8.08 (d, J=8.21 Hz, 1 H),8.19 (d, J=8.60 Hz, 1 H).HPLC/MS (9 min) retention time 5.45 min.LRMS: m/z 224 (M+1).
68%
Stage #1: With dibromo sulfoxide In toluene at 110℃; for 1 h; Stage #2: With potassium carbonate In water
The title compound of Preparation 29 (3.68 g, 23.1 mmol) was suspended in 60 ml toluene. Thionyl bromide (12.0 g, 57.8 mmol) was slowly added and the mixture was heated at 110C for 1 h. The mixture was concentrated under reduced pressure and the residue was partitioned between water and dichloromethane. The aqueous phase was basified with potassium carbonate and extracted three times with dichloromethane. The combined organics were washed with water, brine and dried over sodium sulphate and evaporated. The residue was purified by column chromatography (ethyl acetate-hexane, 5:95) to give 3.5 g (15.8 mmol, 68percent) of the title compound as a solid. Purity 100percent. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.72 (s, 2 H), 7.54 - 7.62 (m, 2 H), 7.70 - 7.79 (m, 1 H), 7.83 (d, J=8.21 Hz, 1 H), 8.08 (d, J=8.21 Hz, 1 H), 8.19 (d, J=8.60 Hz, 1 H). HPLC/MS (9 min) retention time 5.45 min. LRMS: m/z 224 (M+1).
Reference：
[1] Tetrahedron Letters, 2013, vol. 54, # 38, p. 5211 - 5213
[2] Tetrahedron, 1999, vol. 55, # 41, p. 12069 - 12078
[3] Tetrahedron, 2013, vol. 69, # 44, p. 9322 - 9328
[4] Tetrahedron Asymmetry, 2009, vol. 20, # 14, p. 1672 - 1682
[5] Patent: WO2012/69175, 2012, A1, . Location in patent: Page/Page column 42-43
[6] Patent: EP2457900, 2012, A1, . Location in patent: Page/Page column 25; 26
[7] Tetrahedron Letters, 2012, vol. 53, # 35, p. 4747 - 4750
[8] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4364 - 4374
[9] Chemistry - An Asian Journal, 2017, vol. 12, # 2, p. 239 - 247
With sodium tetrahydroborate; In tetrahydrofuran; at 20 - 35℃; for 0.5h;
Methyl quinoline 2-carboxylate 2 (5 g, 26.8 mmol) in solution in THF (30 mL) was added, at room temperature, to a solution of NaBH4 (710 mg, 18.8 mmol) in THF (20 mL). The mixture was stirred at 35 C for 30 min. Then, at 35 C, methanol (2.5 mL) was added followed by warm water (30 mL), and finally ethyl acetate (20mL). The organic layer was washed with water (2×30 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude yellow-blue residue was purified through a silica gel column chromatography (AcOEt/MCH: 60/40). White solid; 73% yield; mp 135 C (dec); 1H NMR (300 MHz, CDCl3) 4.68 (1H, s, OH), 4.95 (2H, s, CH2), 7.31 (1H, m, CHar), 7.55 (1H, m, CHar), 7.71 (1H, m, CHar), 7.81 (1H, m, CHar), 8.10 (2H, m, CHar); 13C NMR (75 MHz, CDCl3) 64.25, 118.43, 126.35, 127.55, 127.69, 128.57, 129.81, 136.86, 146.72, 159.19; Anal. Calcd. for C10H9NO C, 75.45; H, 5.70; N, 8.80. Found C, 75.13; H, 5.56; N, 8.75.
With sodium hydroxide; water; In tetrahydrofuran; methanol; at 20℃; for 1h;
A mixture of 2-chloromethylquinoline hydrochloride (21.4 g), sodium acetate (32.8 g) and N,N-dimethylformamide (200 ml) was stirred at 60C overnight. After cooling, the reaction solution was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. A mixture of the residue, 4N aqueous sodium hydroxide solution (50 ml), tetrahydrofuran (100 ml) and methanol (100 ml) was stirred at room temperature for 1 hour, and poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to obtain 2-quinolylmethanol (14.0 g, yield 88%) as colorless crystals from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). This was recrystallized from ethyl acetate-hexane. Melting point: 68-69C
Malonic acid (2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester quinolin-2-ylmethyl ester[ No CAS ]
With hydrogen;5% palladium over charcoal; In tetrahydrofuran; ethanol; at 40℃; for 48h;
Preparation LXIII 4-Hydroxymethyl-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline [0409] 2-hydroxymethyl-1,2,3,4-tetrahydroquinoline [0410] Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0 C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and <strong>[1780-17-2]2-(hydroxymethyl)quinoline</strong>. A solution of the recovered <strong>[1780-17-2]2-(hydroxymethyl)quinoline</strong> in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40 C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. [0411] 1H NMR (400 MHz, CDCl3) delta 1.641.74 (m, 1H), 1.851.91 (m, 1H), 1.42.3 (br, 2H), 2.682.75 (m, 1H), 2.782.85 (m, 1H), 3.403.46 (m, 1H), 3.513.56 (m, 1H), 3.73 (dd, J1=3.91 Hz, J2=10.26 Hz, 1H), 6.51 (dd, J1=1.0 Hz, J2=7.83 Hz, 1H), 6.61 (dt, J1=1.0 Hz, J2=7.33 Hz, 1H), 6.936.98 (m, 2H). [0412] Ring Formation/Decarboxylation [0413] Beginning with 2-hydroxymethyl-1,2,3,4-tetrahydroquinoline, the title compound was prepared essentially as described in Preparation I. [0414] MS (ES, m/z)188.1 (M++1), 186.1 (M+-1)
With sodium hydride; In DMF (N,N-dimethyl-formamide); at 0℃; for 1h;
Sodium hydride (60%, oily, 1.58g) was added to a solution of <strong>[1780-17-2]2-quinolylmethanol</strong> (6.29 g) and methyl 6-chloro-3-pyridinecarboxylate (6.78g) in N,N-dimethylformamide (100 ml) at 0C, and the mixture was stirred for 1 hour. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. Lithium aluminium hydride (1.50 g) was added to a solution of the residue in tetrahydrofuran (150 ml) at 0C, which was stirred at room temperature for 10 minutes. Sodium sulfate decahydrate (12.7 g) was added to the reaction mixture, which was stirred at room temperature for 1 hour. The precipitate was removed by filtration, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography to obtain 2-(2-quinolylmethoxy)-5-pyridylmethanol (5.31 g, yield 50%) as colorless crystals from the fraction eluted with ethyl acetate. This was recrystallized from ethyl acetate-hexane. Melting point: 124-125C
Example 171 (5R)-5-ethyl-9,10,11-trifluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino[3',4':6,7]indolizino[1,2-b]quinoleine-3,15-dione Stages 95a to 95c are applied to 3,4,5-trifluoroaniline and the resulting quinolylmethanol is treated with (+)-EHHOPD according to a procedure of Stage 83h in order to produce the expected compound. NMR 1H (DMSO): 0.87 (t, 3H); 1.83 (q, 2H); 3.07 (d, 1H); 3.45 (d, 1H); 5.26 (s, 2H); 5.39 (d, 1H); 5.51 (d, 1H); 6.03 (s, 1H); 7.40 (s, 1H); 8.09 (m, 1H); 8.86 (s, 1H).
EXAMPLE 171 (5R)-5-ethyl-9,10,11-trifluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino[3',4':6,7]indolizino[1,2-b]quinoleine-3,15-dione Stages 95a to 95c are applied to 3,4,5-trifluoroaniline and the resulting quinolylmethanol is treated with (+)-EHHOPD according to a procedure of Stage 83h in order to produce the expected compound. NMR 1H (DMSO): 0.87 (t, 3H); 1.83 (q, 2H); 3.07 (d, 1H); 3.45 (d, 1H); 5.26 (s, 2H); 5.39 (d, 1H); 5.51 (d, 1H); 6.03 (s, 1H); 7.40 (s, 1H); 8.09 (m, 1H); 8.86 (s, 1H).
Step 232a. N-(2-quinolyl)methoxyphthalimide <strong>[1780-17-2]2-(hydroxymethyl)quinoline</strong> (1.20 g, 7.55 mmol), triphenyl phosphine (1.00 g, 6.29 mmol, 1.05 equiv) and N-hydroxyphthalimide (1.08 g, 6.63 mmol, 1.05 equiv) were dissolved in 25 mL of dry THF. Diethylazodicarboxylate (1.09 mL, 6.93 mmol, 1.10 equiv) was then added dropwise and the reaction was stirred overnight. The reaction mixture filtered to give a white solid. The filtrate was concentrated and a second crop of material was obtained by triturating with Et2 O. This was combined with the original solid and recrystallization from EtOH gave the desired product (1.53 g) as a fluffy white solid. MS(CI) m/e 305 (M+H)+.
EXAMPLE XXII Ethyl 2-cycloheptyl-2-[5-(quinolin-2-ylmethoxy)-thiophen-2-yl]acetate STR30 2-(Hydroxymethyl)quinoline (1.0 g 6.3 mmol) is dissolved in tert-butanol (10 ml) and sodium hydride (0.25 g 6.3 mmol) is slowly added to this solution. The mixture is stirred at 60 C. for 30 minutes and then heated to 100 C. 2.18 g (6.3 mmol) of the compound from Example XII and copper(I) bromide (0.09 g 0.63 mmol) are added and the mixture is stirred overnight at 100 C. As little reaction has taken place, further copper(I) bromide is added (0.81 g, 5.7 mmol). The mixture is again stirred at 100 C. for 3 hours and cooled, CH2 Cl2 and saturated NH4 Cl solution are added and the mixture is extracted. The organic phase is dried over sodium sulphate and concentrated in a rotary evaporator. The residue is purified by column chromatography: Yield: 0.10 g (2%) Rf =0.25 (10:1; petroleum ether:ethyl acetate); mass (calculated) for C25 H29 NO3 S=423.57; mass spectrum (FAB, rel. intensity) 424 (100%), 143 (90%).
3-(1-Hydroxyhexyl)benzyl p-toluene sulfonate[ No CAS ]
2-(3-(1-hydroxyhexyl)benzyloxymethyl)quinoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With triethylamine; In dichloromethane;
EXAMPLE 28 2-(3-(1-Hydroxyhexyl)benzyloxymethyl)quinoline A mixture of <strong>[1780-17-2]2-hydroxymethylquinoline</strong> (8 g, 0.05 mol) and 3-(1-hydroxyhexyl)benzyl p-toluenesulfonate (18.2 g, 0.05 mol; prepared as in Example 17) in methylene chloride (200 ml) containing triethylamine (15 ml) was stirred at 0 C. for 4 hours, and then allowed to warm up to room temperature. This mixture was stirred for two more hours at this temperature, and then poured into water. The organic layer was separated and washed with dilute sodium hydroxide solution, water and brine. After drying the organics, all volatiles were removed to obtain the crude product as a yellowish brown liquid. This was purified by chromatography on silica gel using 15% ethyl acetate in hexanes to get the pure product as a clear, light yellow liquid (9 g, 52% yield).
With tributylphosphine; In tetrahydrofuran; di-isopropyl ether; ethyl acetate;
Reference Example 1 To tert-butyl 3-hydroxy-4-propyl-1H-pyrazole-1-carboxylate (8.88 g), (quinolin-2-yl)methanol (6.25 g) and tributylphosphine (20 ml) in tetrahydrofuran (200 ml) was added 1,1'-azodicarbonyldipiperidine (19.8 g), and the mixture was stirred at 60C for 2 hr. The reaction mixture was concentrated, diisopropyl ether was added, and the precipitated crystals were filtered off. The filtrate was concentrated, and the obtained residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (2:1, v/v). The elude was concentrated. To a solution of the obtained oil in ethyl acetate (150 ml) was added 4N hydrogen chloride-ethyl acetate (150 ml), and the mixture was stirred overnight at room temperature. The reaction mixture was poured into saturated aqueous sodium hydrogencarbonate (400 ml), and the organic layer was separated. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The obtained crystals were collected by filtration while washing with hexane and dried to give 2-[(4-propyl-1H-pyrazol-3-yl)oxy]methyl}quinoline as colorless crystals (5.73 g, yield 55%). melting point 94 - 95C.
3-(quinolin-2-ylmethoxy)-phthalic acid dimethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h;
Step 2:[208] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and quinolin-2-yl- methanol (0.76 g, 4.8 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropylazodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3- hydroxy-phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the mixture was filtered. The filter was washed with ethyl acetate (25 mL) and the combined filtrates were evaporated.
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; for 20h;
15.1 ethyl 1-[(quinolin-2-yl)methyl]-5-trifluoro-methyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylate 0.14 g (0.871 mmol) of (quinolin-2-yl)methanol, 0.228 g (0.871 mmol) of triphenylphosphine and 0.151 g (0.871 mmol) of diethyl azodicarboxylate (DEAD) are added, with stirring, to a suspension of 0.15 g (0.581 mmol) of ethyl 5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (Nazare, M. et al., Angewandte Chemie, International Ed., 2004, 43(34), 4526-4528) in 2 ml of dry tetrahydrofuran. After stirring at ambient temperature for 20 h, the reaction mixture is concentrated under reduced pressure and the resulting product is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and heptane. 0.18 g of the expected product is thus obtained in the form of a yellow oil.
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 18h;Inert atmosphere; Sealed tube;
Example XVIIXVI XVI lCompound XVI (35 mg), PPh3 (30 mg), and quinolin-2-yl-methanol (18 mg) were placed in a vial and the vial was purged with nitrogen. THF (700 muL) was added and the reaction was cooled to 0 0C. DEAD (20 mg) in 100 muL of THF was added dropwise and the reaction allowed to stir at ambient temperature for 18 h. The solvent was evaporated and the residue purified via column chromatography (0-10% MeOH-NH3ZDCM) to give XVII as a white solid (34 mg). LCMS (ESI) 3.09 min (449, M+H).
2-[(3-phenyl-3H-imidazo[4,5-b]pyridin-5-yl)oxy]methyl}quinoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 60℃; for 15h;
To a mixture of 20 (211 mg, 1.00 mmol) and <strong>[1780-17-2]2-quinolinylmethanol</strong> (260 mg, 1.63 mmol) in THF (10 mL) were added 1,1'-(azodicarbonyl)dipiperidine (ADDP, 378 mg, 1.50 mmol) and tributylphosphine (0.37 mL, 1.50 mmol), and the mixture was stirred at 60 C for 15 h. After cooling at room temperature, the mixture was concentrated in vacuo, and the residue was purified by silica gel column chromatography (0-5% MeOH in CHCl3) to give free form of the title compound, which was dissolved in CHCl3 (10 mL) and 4 M HCl/EtOAc (1.0 mL, 4.0 mmol) was added to the solution. The mixture was concentrated in vacuo and the residue was recrystalized from EtOH-Et2O to give a beige solid.
With silver(l) oxide; In 1,4-dioxane; at 20℃; for 24h;
General procedure: Freshly prepared Ag2O (2.20 mmol) was added at room temperature to a solution of pyridin-2-ylmethanol (1.00 mmol) and 2-iodopropane (2.20 mmol) in 1,4-dioxane (10 mL) and stirred for 24 h. The reaction mixture was filtered through a Celite bed and washed with ethyl acetate. Filtrate was concentrated under vacuum.The resulting material was purified by flash chromatography on a Biotage instrumentusing 4-g flash cartridge and eluted with 12-15% ethyl acetate in hexane to give isopropyl picolinate (2) (65% yield).
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran;
<strong>[1780-17-2]2-(hydroxymethyl)quinoline</strong> (1.20 g, 7.55 mmol), triph-enyl phosphine (1.00 g, 6.29 mmol, 1.05 equiv) and N-hydroxyphthalimide (1.08 g, 6.63 mmol, 1.05 equiv) were dissolved in 25 mL of dry THF. Diethylazodicarboxylate 50 (1.09 mL, 6.93 mmol, 1.10 equiv) was then added dropwise and the reaction was stirred overnight. The reaction mixture filtered to give a white solid. The filtrate was concentrated and a second crop of material was obtained by triturating with Et20. This was combined with the original solid and 55 recrystallization from EtOH gave the desired product (1.53 g) as a fluffy white solid.
With 5,10,15,20-tetraphenyl-21H,23H-porphine; copper chromite; trifluorormethanesulfonic acid; nitratobis(triphenyl phosphine)copper(I); silver(I) triflimide; In 1,4-dioxane; dimethyl sulfoxide; at 70℃; for 12h;
To a suitable amount of an organic solvent (a mixture of 1,4-dioxane and dimethylsulfoxide (DMSO) in a volume ratio of 1: 3) at room temperature,100 mmol of the compound of the above formula (I)150 mmol of the compound of the above formula (II)10 mmol of catalyst (a mixture of 3.3 mmol of bis (triphenylphosphine) cuprous nitrate (Cu (PPh3) 2NO3) and 6.7 mmol of tetraphenylporphyrin)180 mmol of oxidizer copper chromite,5 mmol of accelerator AgNTf2 and 40 mmol of trifluoromethanesulfonic acid as an acid promoter were added and the temperature was raised to 70C and the reaction was stirred at that temperature for 12 hours.After completion of the reaction, the pH of the filtrate was adjusted to neutral by filtration while hot, and saturatedSodium carbonate aqueous solution to wash the full 2-3 times, then add acetone extraction 2-3 times, combine the organic phase,Dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography through 300-400 mesh,Was washed with an equal volume ratio of chloroform-ethyl acetate mixture to give the compound of formula (III) aboveThe yield was 97.2%.
With 5,10,15,20-tetraphenyl-21H,23H-porphine; copper chromite; trifluorormethanesulfonic acid; nitratobis(triphenyl phosphine)copper(I); silver(I) triflimide; In 1,4-dioxane; dimethyl sulfoxide; at 80℃; for 10h;
in room temperature,To a suitable amount of an organic solvent (a mixture of 1,4-dioxane and dimethylsulfoxide (DMSO) in a volume ratio of 1: 3)100 mmol of the compound of the above formula (I)175 mmol of the compound of the above formula (II)15 mmol of a catalyst (a mixture of 4.3 mmol of bis (triphenylphosphine) cuprous nitrate (Cu (PPh3) 2NO3) and 10.7 mmol of tetraphenylporphyrin)200 mmol oxidizer copper chromite,7 mmol accelerator AgNTf2 and 60 mmol acidic agent trifluoromethanesulfonic acid,Then the temperature was raised to 80 C, and the reaction was stirred at that temperature for 10 hours;After completion of the reaction, the pH of the filtrate was adjusted to neutral by filtration while hot, and saturatedSodium carbonate aqueous solution to wash the full 2-3 times, then add acetone extraction 2-3 times, combine the organic phase,Dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography through 300-400 mesh,Was washed with an equal volume ratio of chloroform-ethyl acetate mixture to give the compound of formula (III) aboveThe yield was 96.9%.
diphenyloxophosphinyl(quinolin-2-yl)methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With dipotassium peroxodisulfate; In acetone; at 40℃;
(1) <strong>[1780-17-2]2-hydroxymethylquinoline</strong> (0.127 g, 0.8 mmol) was added to the reaction flask,Diphenylphosphine oxide (0.242 g, 1.2 mmol),Potassium persulfate (0.432 g, 1.6 mmol) and acetone (2 mL)40 C reaction; (2) TLC tracking reaction until complete; (3) The crude product obtained after the completion of the reaction was separated by column chromatography (dichloromethane: methanol = 40: 1)The target product was obtained (yield 76%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
