Name: 73568-26-0|2-Chloro-8-methylquinoline-3-carbaldehyde|98%
Brand: Ambeed
SKU: A383051
Price: 12.0 USD
Availability: InStock
Rating: 96 (35 reviews)

1
[ 73568-26-0 ]
[ 101382-54-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydrogenchloride for 1h; Heating;
86.5%	With hydrogenchloride; glacial acetic acid for 3h; Reflux;	2.2.11. Synthesis of 8-Methyl-2-oxoquinoline-3-carbaldehyde(15). 2-Chloro-8-methylquinoline-3-carbaldehyde (0.5 g,0.0024 mol) was added to a mixture of 6M HCl (10 mL) andglacial acetic acid (10 mL). +e mixture was reBuxed for3 hours, at which the TLC analysis showed complete disappearanceof the starting material. +en the acetic acidmixture was removed with distillation under reducedpressure. +e solid residue was washed with cold water andallowed to dry in wood cupboard. +e amount of theproduct was 395 mg. Yield 86.5%; yellow powder; mp176-178°C; Rf 0.41 (n-hexane:EtOAc 1 : 1); UV-Vis +max(MeOH) 375 nm; IR (cm-1, KBr) 3429 (O-H str.), 3179.5(NH str.), 3023 (aromatic C-H), 2919.8 (aliphatic CH-str’.),2837.2 (aliphatic C-H) 1673 (CO str.), 1610 (quinoline CN str.), 1558 and 1465 (aromatic CC str.); 1H NMR(400 MHz; CDCl3) ,δH 2.56 (3H, s, C-10), 7.23 (1H, t,J 7.5 Hz, H-6), 7.51 (1H, d, J 7.32 Hz, H-7) 7.61 (1H, m,J 7.7 Hz, H-5), 8.49 (1H, s, H-4) and 10.48 (1H, s, H-9); 13CNMR (100 MHz, CDCl3) ,δC 16.7 (C-10), 117.9 (C-6), 123.3(C-3, C-8), 129.1 (C-4a, C-7), 135.0 (C-5), 139.1 (C-8a),144.2 (C-4), 162.7 (C-2), 190.00 (C-9).
69%	With lithium hydroxide monohydrate; glacial acetic acid at 90℃; for 8h;

	With hydrogenchloride Heating;
	With hydrogenchloride
	With glacial acetic acid Heating;
	With hydrogenchloride In 1,4-dioxane for 4h; Heating / reflux;	4 Example 4 N-(3-methoxypropyl)-4-methyl-N-((8-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide A mixture of 2-chloro-8-methylquinoline-3-carboxaldehyde (8 g, 39 mmol) and 6N HCl (350 mL, 2.7 mol) in dioxane (350 mL) was heated at reflux for 4 h and cooled to the room temperature. The formed precipitate was filtered, washed with MeOH and ether, then dried in vacuo to provide 8-methyl-2-oxo-1,2-dihydro-quinoline-3-carbaldehyde (6.9 g), as a yellow solid.
	With glacial acetic acid In lithium hydroxide monohydrate Reflux;	Synthesisof quinoline-3-carbaldehydes 16a-e General procedure: A suspension of aldehyde 15 (1 mmol) in 70% aqueous acetic acid (10 mL) was heated under reflux for 4-6 h (see ref 5 in article). Completion of the reaction was checked by TLC. After cooling a solid product precipitated which was filtered, washed well with water, dried and purified by recrystallization from DMF.
	With hydrogenchloride In lithium hydroxide monohydrate for 3h; Reflux;
	With glacial acetic acid Reflux;
	With lithium hydroxide monohydrate; glacial acetic acid Reflux;
	With lithium hydroxide monohydrate; glacial acetic acid at 95℃; for 10h;
	With glacial acetic acid Reflux;
	With glacial acetic acid In lithium hydroxide monohydrate at 95℃; for 10h;
	With lithium hydroxide monohydrate; glacial acetic acid at 70 - 95℃;	General procedure for the synthesis of quinolonederivatives (7a-d) General procedure: 2-Chloro-3-formyl quinoline derivatives were treated with70% acetic acid (CH3CO2H) aqueous solution (200 mL)Medicinal Chemistry Researchbetween 70 and 95 °C for 12 h. Then the solution wascooled to room temperature and filtered off withoutrecrystallization. The products were obtained inexcellent yield.
	With lithium hydroxide monohydrate; glacial acetic acid at 70 - 95℃;	General procedure for the synthesis of quinolonederivatives (7a-d) General procedure: 2-Chloro-3-formyl quinoline derivatives were treated with70% acetic acid (CH3CO2H) aqueous solution (200 mL)Medicinal Chemistry Researchbetween 70 and 95 °C for 12 h. Then the solution wascooled to room temperature and filtered off withoutrecrystallization. The products were obtained inexcellent yield.
	With lithium hydroxide monohydrate; glacial acetic acid at 90℃; for 12h;
	With glacial acetic acid for 6h; Reflux;

Reference： [1]Tilakraj, T.; Ambekar, Sarvottam Y. [Journal of the Indian Chemical Society, 1985, vol. 62, # 3, p. 251 - 253]
[2]Belay, Zerihun; Eswaramoorthy, Rajalakshmanan; Melaku, Yadessa; Zeleke, Digafie [Journal of Chemistry, 2020, vol. 2020]
[3]Darrell, Oliver T.; Hulushe, Siyabonga T.; Mtshare, Thanduxolo E.; Beteck, Richard M.; Isaacs, Michelle; Laming, Dustin; Hoppe, Heinrich C.; Krause, Rui W.M.; Khanye, Setshaba D. [South African Journal of Chemistry, 2018, vol. 71, p. 174 - 181]
[4]Nithyadevi; Selvi; Rajendran [Phosphorus, Sulfur and Silicon and the Related Elements, 2004, vol. 179, # 11, p. 2355 - 2364] Nithyadevi; Rajendran [Phosphorus, Sulfur and Silicon and the Related Elements, 2005, vol. 180, # 8, p. 1849 - 1862] Nithyadevi; Rajendran [Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 11, p. 2623 - 2634]
[5]Nandha Kumar; Suresh; Mohan [Chemistry of Heterocyclic Compounds, 2004, vol. 40, # 11, p. 1490 - 1492]
[6]Singh, Mrityunjay K.; Chandra, Atish; Singh, Bhawana; Singh, Radhey M. [Tetrahedron Letters, 2007, vol. 48, # 34, p. 5987 - 5990]
[7]Current Patent Assignee: AGRIUS GROUP - US2007/287706, 2007, A1 Location in patent: Page/Page column 32
[8]Laali, Kenneth K.; Insuasty, Daniel; Abonia, Rodrigo; Insuasty, Braulio; Bunge, Scott D. [Tetrahedron Letters, 2014, vol. 55, # 31, p. 4395 - 4399]
[9]Guenfoud, Fatiha; Boulcina, Raouf; Laabassi, Mohammed; Mosset, Paul [Letters in Organic Chemistry, 2014, vol. 11, # 10, p. 736 - 742]
[10]Insuasty, Daniel; Robledo, Sara M.; Vélez, Iván D.; Cuervo, Paola; Insuasty, Braulio; Quiroga, Jairo; Nogueras, Manuel; Cobo, Justo; Abonia, Rodrigo [European Journal of Medicinal Chemistry, 2017, vol. 141, p. 567 - 583]
[11]Abonia, Rodrigo; Gutiérrez, Luisa F.; Insuasty, Braulio; Quiroga, Jairo; Laali, Kenneth K.; Zhao, Chunqing; Borosky, Gabriela L.; Horwitz, Samantha M.; Bunge, Scott D. [Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 642 - 654]
[12]Bazine, Ismahene; Bensegueni, Rafik; Bensouici, Chawki; Boukhari, Abbes; Cheraiet, Zinelaabidine [Journal of Heterocyclic Chemistry, 2020]
[13]Abonia, Rodrigo; Bernal, Anthony; Guzman, Juan; Insuasty, Braulio; Insuasty, Daniel; Marquez, Edgar; Puerto, Gloria; Quiroga, Jairo; Svetaz, Laura; Vidal, Oscar; Zacchino, Susana [Antibiotics, 2019, vol. 8, # 4]
[14]Bazine, Ismahene; Bendjedid, Samira; Boukhari, Abbes [Archiv der Pharmazie, 2021, vol. 354, # 3]
[15]Boukhari, Abbes; Djahoudi, Abdelghani; Litim, Bilal; Meliani, Saida [Medicinal Chemistry Research, 2022, vol. 31, # 1, p. 60 - 74]
[16]Boukhari, Abbes; Djahoudi, Abdelghani; Litim, Bilal; Meliani, Saida [Medicinal Chemistry Research, 2022, vol. 31, # 1, p. 60 - 74]
[17]Mizuta, Satoshi; Otaki, Hiroki; Ishikawa, Takeshi; Makau, Juliann Nzembi; Yamaguchi, Tomoko; Fujimoto, Takuya; Takakura, Nobuyuki; Sakauchi, Nobuki; Kitamura, Shuji; Nono, Hikaru; Nishi, Ryota; Tanaka, Yoshimasa; Takeda, Kohsuke; Nishida, Noriyuki; Watanabe, Ken [Journal of Medicinal Chemistry, 2022, vol. 65, # 1, p. 369 - 385]
[18]Al-Mahmoudy, Amany M. M.; El-Behairy, Mohammed Farrag; El-Kalyoubi, Samar A.; Ibrahim, Tarek S.; Taher, Ehab S. [Pharmaceuticals, 2022, vol. 15, # 5]

2
[ 120-66-1 ]
[ 68-12-2 ]
[ 73568-26-0 ]

Yield	Reaction Conditions	Operation in experiment
72%		General procedure: Dimethylformamide (12 mmol, 3 equiv.) was cooled at 0C in a round flask equipped with a drying tube and phosphorus pentachloride (18 mmol, 4.5 equiv.) was added slowly and the mixture was stirred for 15 minutes keeping the temperature below 0C. To this solution was added in a portion the corresponding acetanilide (4 mmol, 1 equiv.) and the reaction mixture was heated under reflux and stirring for the appropiate time depending of the acetanilide. The resulted mixture was cooled to 0C and the solution was poured slowly into ice-water and stirring for ten minutes, obtaining a yellow solid which was filtered, washed several time with cold water and dried under vacuum. The 2-chloroquinoline-3-carbaldehydes were recrystallized according to the literature.
68%		INTERMEDIATE 322-Chloro-8-methylquinoline-3-carbaldehydeN,N-Dimethylformamide (51.8 mL, 668 mmol) was added portionwise over 15 minutes, with stirring, to phosphorus oxychloride (175 mL, 1.87 mol) at 0C. The reaction mixture was allowed to warm to room temperature and treated with Intermediate 31 (39.8 g, 267 mmol), then heated to 80C and stirred for 72 h. The reaction mixture was cooled to room temperature, then carefully poured portionwise into a vigorously stirred mixture of ice-water. The ice-water mixture was allowed to warm to room temperature over 30 minutes, then filtered. The precipitate was washed with water and dried under vacuum. The title compound (37.3 g, 68%>) was obtained as a cream-coloured solid. deltaEta (CDC13) 10.50 (s, 1H), 8.73 (s, 1H), 7.83 (d, J 8.1 Hz, 1H), 7.76-7.72 (m, 1H), 7.55 (dd, J 7.9, 7.3 Hz, 1H), 2.81 (s, 3H). LCMS (ES+) 206 (M+H)+, RT 1.54 minutes.
37%		A solution of phosphoryl trichloride (62.4 ml_, 700.0 mmol) in N,N- dimethylformamide (19.2 ml_, 250.0 mmol) was cooled to 0 0C and stirred for 30 min under nitrogen. To this solution N-O-tolylacetamide (14.9 g, 100.0 mmol) was added at 20 0C and the resulted mixture was stirred for 30 min under nitrogen. The temperature of the reaction mixture was slowly raised to 80 0C and stirred for 20 h under nitrogen. Yellow solid precipitated out upon slow addition of crushed ice (300 g) to the reaction mixture. The resulting solid was filtered, washed with water and dried under high vacuum at 60 0C to afford 2-chloro-8-methylquinoline-3-carbaldehyde (7.61 g, 37%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) delta 10.36 (s, 1 H), 8.92 (s, 1 H), 8.08 (d, J = 8.1 Hz, 1 H), 7.82 (d, J = 6.9 Hz, 1 H), 7.61 (t, J = 7.6 Hz, 1 H), 2.65 (s, 3H).

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2005,vol. 44,p. 1868 - 1875
[2]Indian Journal of Heterocyclic Chemistry,2011,vol. 21,p. 61 - 64
[3]Synlett,2000,p. 1115 - 1118
[4]Medicinal Chemistry Research,2012,vol. 21,p. 2340 - 2348,9
[5]Synthetic Communications,2006,vol. 36,p. 3581 - 3589
[6]Synthetic Communications,2016,vol. 46,p. 287 - 291
[7]Patent: WO2012/32334,2012,A1 .Location in patent: Page/Page column 39
[8]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2011,vol. 50,p. 1491 - 1495
[9]Patent: WO2008/113006,2008,A1 .Location in patent: Page/Page column 64
[10]Synthetic Communications,2004,vol. 34,p. 2019 - 2024
[11]Phosphorus, Sulfur and Silicon and the Related Elements,2008,vol. 183,p. 1870 - 1883
[12]Chemical and Pharmaceutical Bulletin,2009,vol. 57,p. 557 - 560
[13]Heterocyclic Communications,2011,vol. 17,p. 111 - 119
[14]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 942 - 944
[15]Journal of Chemical Sciences,2011,vol. 123,p. 645 - 655
[16]Medicinal Chemistry Research,2012,vol. 21,p. 1322 - 1333
[17]Tetrahedron Letters,2014,vol. 55,p. 4395 - 4399
[18]European Journal of Medicinal Chemistry,2014,vol. 83,p. 569 - 580
[19]Letters in Organic Chemistry,2014,vol. 11,p. 736 - 742
[20]Medicinal Chemistry,2015,vol. 11,p. 580 - 589
[21]Journal of Agricultural and Food Chemistry,2015,vol. 63,p. 5587 - 5596
[22]Research on Chemical Intermediates,2015,vol. 41,p. 5509 - 5519
[23]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 2278 - 2283
[24]MedChemComm,2016,vol. 7,p. 1832 - 1848
[25]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1696 - 1703
[26]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 2740 - 2747
[27]Journal of Sulfur Chemistry,2018,vol. 39,p. 435 - 442
[28]Letters in drug design and discovery,2018,vol. 15,p. 914 - 922
[29]Journal of Heterocyclic Chemistry,2020
[30]Bioorganic Chemistry,2020,vol. 99

3
[ 73568-26-0 ]
[ 51347-93-4 ]
<i>N</i>-(2-chloro-8-methyl-quinolin-3-ylmethylene)-<i>N</i>'-(3-chloro-quinoxalin-2-yl)-hydrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In N,N-dimethyl-formamide at 20℃; for 3h;

Reference： [1]Reddy, G. Jagath; Latha; Thirupathaiah [Heterocyclic Communications, 2003, vol. 9, # 3, p. 243 - 246]

4
[ 13336-31-7 ]
[ 73568-26-0 ]
2-[1-(2-Chloro-8-methyl-quinolin-3-yl)-meth-(E)-ylidene]-4-methoxy-indan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium methylate In methanol at 20℃;

Reference： [1]Charris, Jaime E.; Dominguez, Jos N.; Gamboa, Neira; Rodrigues, Juan R.; Angel, Jorge E. [European Journal of Medicinal Chemistry, 2005, vol. 40, # 9, p. 875 - 881]

5
[ 6412-87-9 ]
[ 73568-26-0 ]
6-[1-(2-Chloro-8-methyl-quinolin-3-yl)-meth-(E)-ylidene]-6,7-dihydro-indeno[5,6-d][1,3]dioxol-5-one [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 875 - 881

6
[ 24644-78-8 ]
[ 73568-26-0 ]
2-[1-(2-Chloro-8-methyl-quinolin-3-yl)-meth-(E)-ylidene]-4-methyl-indan-1-one [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 875 - 881

7
[ 6850-57-3 ]
[ 73568-26-0 ]
[ 917746-08-8 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: 2-methoxybenzylamine With sodium cyanoborohydride In methanol at 20℃; for 0.5h; Molecular sieve; Stage #2: 2-chloro-8-methyl-quinoline-3-carbaldehyde In methanol at 20℃; for 16h;	3 To a stirred solution of (2-methoxyphenyl)methanamine (2.89 g, 21.1 mmol) in methanol (15 mL) were added sodium cyanoborohydride (1.32 g, 21.1 mmol) and molecular sieves (1.00 g) at ambient temperature and the resulted mixture was stirred for 30 min under nitrogen. To this mixture 2-chloro-8-methylquinoline-3-carbaldehyde (3.61 g, 17.6 mmol) was added. The resultant mixture was stirred at ambient temperature for 16 h and concentrated in vacuo to dryness. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/6) to afford 1-(2-chloro- 8-methylquinolin-3-yl)-λ/-(2-methoxybenzyl)methanamine (3.43 g, 59%) as a colorless solid: 1H NMR (300 MHz, CDCI3) δ 8.20 (s, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 7.0 Hz, 1 H), 7.41 (dd, J = 7.7 Hz, 1 H), 7.30-7.20 (m, 2H), 6.92 (dd, J = 7.4, 7.4 Hz, 1 H), 6.87 (d, J = 8.1 Hz, 1 H), 4.00 (s, 2H), 3.87 (s, 2H), 3.82 (s, 3H), 2.75 (s, 3H), 2.12 (s, 2H); 13C NMR (75 MHz, CDCI3) £ 157.6, 149.6, 146.0, 137.7, 136.3, 131.4, 129.98, 129.96, 128.5, 127.7, 127.4, 126.7, 125.3, 120.5, 110.2, 55.2, 50.2, 48.9, 17.8; MS (ES+) m/z 327.1 (M + 1 ).

Reference： [1]Current Patent Assignee: XENON PHARMACEUTICALS INC - WO2008/113006, 2008, A1 Location in patent: Page/Page column 65

8
[ 73568-26-0 ]
[ 536-74-3 ]
[ 1100051-01-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;
80%	With triethylamine; triphenylphosphine; palladium dichloride In acetonitrile at 80℃; for 4h; Inert atmosphere;
	With triethylamine; triphenylphosphine; palladium dichloride In acetonitrile at 80℃;

	With triethylamine; triphenylphosphine; palladium dichloride In acetonitrile at 80℃;
	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃;
	With triethylamine; triphenylphosphine; palladium dichloride In acetonitrile at 80℃; Inert atmosphere;	General procedure for synthesis of starting materials (1) General procedure: Solution of 2-chloroquinoline-3-carbaldehyde (0.25 mmol), phenyl acetylene (0.26 mmol), PdCl2 (4 mol %), PPh3 (8 mol %), CH3CN (4 mL) and TEA (0.5 mmol) was stirred under N2 at 80°C for 1.5-6 h (as monitored by TLC). The reaction mixture was concentrated in vacuo and residue obtained was purified by column chromatography hexane: ethyl acetate to afford 1 (a-o).

Reference： [1]Win, Khin Myat Noe; Sonawane, Amol D.; Koketsu, Mamoru [Organic and Biomolecular Chemistry, 2019, vol. 17, # 40, p. 9039 - 9049]
[2]Location in patent: experimental part Chandra, Atish; Singh, Bhawana; Upadhyay, Shraddha; Singh, Radhey M. [Tetrahedron, 2008, vol. 64, # 51, p. 11680 - 11685]
[3]Location in patent: scheme or table Singh, Bhawana; Chandra, Atish; Singh, Seema; Singh, Radhey M. [Tetrahedron, 2011, vol. 67, # 2, p. 505 - 511]
[4]Sharma, Neha; Asthana, Mrityunjaya; Nandini, Durgesh; Singh; Singh, Radhey M. [Tetrahedron, 2013, vol. 69, # 7, p. 1822 - 1829]
[5]Abbasi Kejani, Alireza; Ansari, Farzaneh; Armaghan, Mahsa; Balalaie, Saeed; Frank, Walter; Jafarpour, Farnaz; Khosravi, Hormoz [Organic and Biomolecular Chemistry, 2021, vol. 19, # 19, p. 4263 - 4267]
[6]Singh, Rashmi; Gupta, Tanu; Sharma, Vishal Prasad; Singh, Radhey M.; Tewari, Ashish Kumar [Tetrahedron, 2021, vol. 99]

9
[ 73568-26-0 ]
[ 26028-65-9 ]
[ 1134633-74-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine In ethanol Reflux;

Reference： [1]Location in patent: experimental part Kalluraya, Balakrishna; Nayak, Janardhana; Adhikari, Adithya; Sujith; Shetty, N. Sucheta; Winter, Manuela [Phosphorus, Sulfur and Silicon and the Related Elements, 2008, vol. 183, # 8, p. 1870 - 1883]

10
[ 73568-26-0 ]
[ 145214-05-7 ]
[ 1167542-08-6 ]

Yield	Reaction Conditions	Operation in experiment
34%	tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 100℃; for 2.75h;microwave irradiation;	To a solution of 2-chloro-8-methylquinoline-3-carboxaldehyde (250 mg, 1.21 mmol) in DME (3 mL) was added <strong>[145214-05-7]2-(tributylstannyl)oxazole</strong> (0.31 mL, 1.76 mmol) and Pd(PPh3 )4 (70 mg, 0.06 mmol). The reaction mixture was heated in a microwave at 1000C for 45 minutes. More Pd(PPh3)4 (50 mg, 0.04 mmol) was added to the mixture, which was heated at 1000C for 2 h. Purification by column chromatography (SiO2, 0- 100% EtOAc in heptane) gave the title compound as a cream solid (99 mg, 34%). 8R (DMSO-d6) 10.85 (s, IH), 8.91 (s, IH), 8.52 (d, J0.6 Hz, IH), 8.12 (d, J8.1 Hz, IH), 7.86 (d, J 7.0 Hz, IH), 7.64-7.72 (m, 2H), 2.81 (s, 3H). LCMS (ES+) 239 (M+H)+, RT 3.65 minutes (Method 3).

Reference： [1]Patent: WO2009/81105,2009,A2 .Location in patent: Page/Page column 35

11
[ 73568-26-0 ]
[ 75-16-1 ]
[ 1017402-89-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde; methylmagnesium bromide In tetrahydrofuran; diethyl ether at -78 - 20℃; for 2h; Stage #2: With water; ammonium chloride In tetrahydrofuran; diethyl ether at 20℃;	99 To a suspension of 2-chloro-8-methylquinoline-3-carboxaldehyde (10 g, 48.6 mmol) in dry THF (100 mL) under nitrogen cooled to -78°C was added dropwise over 1 h methylmagnesium bromide (40 mL, 121.6 mmol, 3.0M solution in Et2O). The reaction was allowed to warm to r.t. and stirred for a further 1 h before being poured slowly into NH4Cl solution (100 mL). The mixture was extracted with EtOAc (2 x 200 mL) and the organic layers were combined, dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as an off-white solid (8.0 g, 74%). δH (CDCl3) 8.33 (s, IH), 7.68 (d, J 8.0 Hz, IH), 7.55 (d, J 7.2 Hz, IH), 7.44 (t, J 7.6 Hz, IH), 5.34-5.40 (m, IH), 2.77 (s, 3H), 1.61 (d, J6.4 Hz, 3H). LCMS (ES+) 222, 224 (M+H)+, RT 3.01 minutes {Method 5).

Reference： [1]Current Patent Assignee: UCB - WO2009/81105, 2009, A2 Location in patent: Page/Page column 64

12
[ 6165-69-1 ]
[ 73568-26-0 ]
[ 1167541-98-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium carbonate In 1,4-dioxane; water at 100℃; for 1h; microwave irradiation;	10 A mixture of 2-chloro-8-methylquinoline-3-carboxaldehyde (258 mg, 1.26 mmol), 3-thiopheneboronic acid (193 mg, 1.51 mmol), K2CO3 (260 mg, 1.88 mmol), palladium(II) acetate (5.6 mg, 0.025 mmol) and triphenylphosphine (26.3 mg, 0.10 mmol) in water (2 mL) was degassed. 1 ,4-Dioxane (6 mL) was added and the mixture further degassed, then heated at 1000C for 1 h under microwave irradiation. The reaction mixture was diluted with DCM (30 mL) and water (10 mL). The organic layer was separated, dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 10% EtOAc in heptane) gave the title compound (297 mg, 93%) as a colourless crystalline solid. δH (CDCl3) 10.40 (s, IH), 8.75 (s, IH), 7.83 (d, J9 Hz, IH), 7.60-7.73 (m, 3H), 7.46-7.54 (m, 2H), 2.85 (s, 3H). LCMS (ES+) 254.2 (M+H)+, RT 4.29 minutes (Method 3).
89%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane at 90℃;

Reference： [1]Current Patent Assignee: UCB - WO2009/81105, 2009, A2 Location in patent: Page/Page column 34
[2]Sonawane, Amol D.; Garud, Dinesh R.; Udagawa, Taro; Kubota, Yasuhiro; Koketsu, Mamoru [New Journal of Chemistry, 2018, vol. 42, # 18, p. 15315 - 15324]

13
[ 73568-26-0 ]
[ 196929-78-9 ]
[ 1167543-87-4 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-2-methylpropane-2-sulfinamide In tetrahydrofuran at 20℃; for 72h;	102 To a solution of 2-chloro-8-methylquinoline-3-carboxaldehyde (2.05 g, 10 mmol) in dry THF (20 mL) under nitrogen was added titanium isopropoxide (5.68 g, 20 mmol) and the mixture stirred at r.t. for 10 minutes. (i?)-(+)-2-Methyl-2-propanesulfinamide (1.21 g, 10 mmol) was added to the reaction which was stirred at r.t. for 72 h. Water (20 mL) was added and the mixture was extracted with DCM (150 mL). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo to afford the title compound as a pale yellow solid (2.4 g, 72%). δH (CDCl3) 9.12 (s, IH), 8.79 (s, IH), 7.78 (d, J 8.4 Hz, IH), 7.67 (d, J 6.8 Hz, IH), 7.51 (t, J 7.8 Hz, IH), 2.79 (s, 3H), 1.32 (s, 9H). LCMS (ES+) 309, 311 (M+H)+, RT 3.66 minutes (Method 5).
72%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: (R)-2-methylpropane-2-sulfinamide In tetrahydrofuran at 20℃; for 72h;	3 To a solution of 2-chloro-8-methylquinoline-3-carboxaldehyde (2.05 g, 10 mmol) in dry THF (20 mL) under nitrogen was added titanium isopropoxide (5.68 g, 20 mmol) and the mixture stirred at r.t. for 10 minutes. (/?)-(+)-2-Methyl-2-propanesulfinamide (1.21 g, 10 mmol) was added to the reaction which was stirred at r.t. for 72 h. Water (20 mL) was added and the mixture was extracted with DCM (150 mL). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo to afford the title compound (2.4 g, 72%) as a pale yellow solid. δH (CDCl3) 9.12 (s, IH), 8.79 (s, IH), 7.78 (d, J8.4 Hz, IH), 7.67 (d, J6.8 Hz, IH), 7.51 (t, J7.8 Hz, IH), 2.79 (s, 3H), 1.32 (s, 9H). LCMS (ES+) 309, 311 (M+H)+.
72%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: (R)-2-methylpropane-2-sulfinamide In tetrahydrofuran at 20℃; for 72h;	INTERMEDIATE 1fi?>;2-Methylpropane-2-sulfmic acid 1 -f2-chloro-8-methylqumolin-3-yl)meth-(.gr)- ylideneamideTo a solution of 2-chloro-8-methylquinoline-3-carboxaldehyde (2.05 g, 10 mmol) in dry THF (20 mL) under nitrogen was added titanium isopropoxide (5.68 g, 20 mmol) and the mixture stirred at r.t. for 10 minutes. (i?)-(+)-2-Methyl-2-propanesulfinamide (1.21 g, 10 mmol) was added to the reaction which was stirred at r.t. for 72 h. Water (20 mL) was added and the mixture was extracted with DCM (150 mL). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo to afford the title compound (2.4 g, 72%) as a pale yellow solid. δH (CDCl3) 9.12 (s, IH), 8.79 (s, IH), 7.78 (d, J8.4 Hz, IH), 7.67 (d, J6.8 Hz, IH), 7.51 (t, J7.8 Hz, IH), 2.79 (s, 3H), 1.32 (s, 9H). LCMS (ES+) 309, 311 (M+H)+.

Reference： [1]Current Patent Assignee: UCB - WO2009/81105, 2009, A2 Location in patent: Page/Page column 65
[2]Current Patent Assignee: UCB - WO2010/92340, 2010, A1 Location in patent: Page/Page column 31
[3]Current Patent Assignee: UCB - WO2010/100405, 2010, A1 Location in patent: Page/Page column 30

14
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[ 333408-31-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde With sodium tetrahydroborate In tetrahydrofuran at 20℃; for 2h; Stage #2: With sodium hydrogencarbonate In water	To a stirred solution of 2-chloro-8-methylquinoline-3-carboxaldehyde (1, 7.59 g, 36.9 mmol) in THF (150 mL) was added NaBHj (1-40 g, 37.0 mmol) and the reaction mixture was stirred at rt for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was triturated with satd. NaHC03 (aq., 200 mL). Precipitates were collected by filtration, washed with H20, and dried under high vacuum to give the alcohol (7.47 g, 97%) as a white solid. MS (EI) for C, ,Hi0ClNO, found 208 (MH+).
96%	With sodium tetrahydroborate; water at 20℃; for 0.0161111h;
94%	With sodium tetrahydroborate In methanol at 20℃;

87%	With methanol; C₂₅H₂₉ClNO₂Rh; caesium carbonate at 90℃; for 1h;
84%	With methanol; sodium tetrahydroborate at 20℃; for 0.5h;
82%	With methanol; sodium tetrahydroborate at 20℃; for 0.5h;	4.1.1. Synthesis of 2-chloro-3-(hydroxymethyl)-8-methylquinoline 2 To a solution of 1 (2.05 g, 0.01 mol) in absolute methanol (50 ml), solid NaBH4 (0.46 g, 0.012 mol) was added portion wise over a period of 30 min with constant stirring at room temperature. The solvent was evaporated under reduced pressure and the residue was triturated with water (25 ml), when the crystalline solid separated out which was filtered, washed with water and dried. The product was recrystallized from methanol to give colourless to cream colored crystals.Yield: 82%; m.p.: 167-168 °C; IR (KBr) cm-1; 3617 (OH), 1623 (CC), 1599 (CN), 758 (C-Cl). 1H NMR (300 MHz, DMSO-d6) δ; 2.74 (s, 3H, CH3), 4.68 (s, 2H, CH2), 5.66 (s, 1H, OH, D2O-exchangeble), 7.46-7.51 (t, 1H, H-6, J = 7.5 Hz), 7.60-7.62 (d, 1H, H-7, J = 7.1 Hz), 7.84-7.86 (d, 1H, H-5, J = 7.8 Hz), 8.37 (s, 1H, H-4). 13C NMR (75 MHz, DMSO-d6) δ; 17.39 (CH3), 59.88 (CH2), 125.71, 126.91, 127.19, 130.01, 133.60, 135.22, 136.15, 145.10, 147.45. FAB-MS; m/z 208 (M+), 210 (M+2). Anal. Calcd. for C11H10ClNO: C, 63.62; H, 4.85; N, 6.75. Found: C, 63.52; H, 4.83; N, 6.78%.
76%	With tricobalt tetraoxide In isopropyl alcohol at 50℃; for 0.5h; Green chemistry; chemoselective reaction;	Transfer hydrogenation of aromatic aldehydes General procedure: The transfer hydrogenation of aldehydes was carried out by stirring mixture of aldehydes, base and catalyst in a magnetic stirrer. To a 5 mLof isopropyl alcohol, 1 mmol of aldehyde, 1 mmol of base and 5 mg of catalyst were added one by one. The mixture was stirred using magnetic stirrer at 500 rpm for 15 min. The reaction was monitored by TLC (Thin layer chromatography) and hydrogenated products were separated by solvent extraction. The extraction involves addition of 30 mL water and 30 mL ethyl acetate to the reaction mixture. The organic layer was separated from aqueous layer and dried. The crude organic layer was subjected into preparative thin layer chromatography for the separation of product using petroleum ether and ethyl acetate as eluents.
	With sodium tetrahydroborate In methanol at 20℃;
	With sodium tetrahydroborate In methanol at 20℃;
	With sodium tetrahydroborate at 20℃; Microwave irradiation;
	With sodium tetrahydroborate In methanol at 20℃;	Preparation of 3-azidomethyl-2-chloro-6/7/8-substituted quinoline (7c-i) General procedure: To a well stirred mixture of 2-chloroquinoline-3-carbaldehyde (2c-i) (0.01 mol) in methanol (10 ml), NaBH4 (0.01 mol) was added in small portions and the mixture was stirred at room temperature for 15-20 min. The completion of the reaction was monitored by TLC and the reaction mixture was concentrated under vacuum. The mixture was poured into ice cold water and the (2-chloroquinolin-3-yl) methanol separated as solid was filtered off and recrystallised from ethyl acetate. (2-Chloroquinolin-3-yl) methanol (0.01 mol) was further dissolved in DCM (10-15 ml) at 5°C and stirred well. After 10-15 min, PBr3 (0.06 mol) was added drop wise and stirred at room temperature for 1 h. After completion of the reaction, DCM was removed under vacuum and the mixture was poured into ice and neutralized by adding a saturated solution of NaHCO3. The precipitate of 3-(bromomethyl)-2-chloroquinoline was filtered and dried. The so formed 3-(bromomethyl)-2-chloro quinoline (0.010 mole) was taken in acetone (20 ml) in a round-bottom flaskamnd to this sodium azide (0.012 mole) in water (3.00 ml) was added drop wise with stirring, which was continued for 10 hr. The reaction mixture was then poured into ice-cold water. 3-Azidomethyl-2-chloro-6/7/8-substituted-quinoline 7c-i separated as solid was filtered and recrystallized using ethanol.
	With sodium tetrahydroborate In methanol at 20℃;

Reference： [1]Current Patent Assignee: EXELIXIS INC - WO2012/37204, 2012, A1 Location in patent: Page/Page column 72; 73
[2]Location in patent: experimental part Roopan, Selvaraj Mohana; Nawaz Khan, Fazlur Rahman [Chemical Papers, 2010, vol. 64, # 6, p. 812 - 817]
[3]Location in patent: experimental part Pokalwar; Hangarge; Kategaonkar; Shingare [Russian Journal of Organic Chemistry, 2009, vol. 45, # 3, p. 430 - 433]
[4]Aboo, Ahmed H.; Bennett, Elliot L.; Deeprose, Mark; Robertson, Craig M.; Iggo, Jonathan A.; Xiao, Jianliang [Chemical Communications, 2018, vol. 54, # 83, p. 11805 - 11808]
[5]Location in patent: experimental part Jawale, Dhanaji V.; Pratap, Umesh R.; Mane, Ramrao A. [Bulletin of the Korean Chemical Society, 2011, vol. 32, # 7, p. 2171 - 2177] Location in patent: experimental part Jawale, Dhanaji V.; Pratap, Umesh R.; Mulay, Aparna A.; Mali, Jyotirling R.; Mane, Ramrao A. [Journal of Chemical Sciences, 2011, vol. 123, # 5, p. 645 - 655]
[6]Location in patent: experimental part Kumar, Suresh; Bawa, Sandhya; Drabu, Sushma; Gupta, Himanshu; MacHwal, Lalit; Kumar, Rajiv [European Journal of Medicinal Chemistry, 2011, vol. 46, # 2, p. 670 - 675]
[7]Krishnaveni; Lakshmi; Kaveri; Kadirvelu [Molecular catalysis, 2020, vol. 496]
[8]Location in patent: scheme or table Mandhane, Priyanka G.; Joshi, Ratnadeep S.; Khan, Wajid; Gill, Charansingh H. [Journal of the Korean Chemical Society, 2011, vol. 55, # 4, p. 656 - 661]
[9]Shaikh, Saba Kauser J.; Kamble, Ravindra R.; Bayannavar, Praveen K.; Somagond, Shilpa M.; Joshi, Shrinivas D. [Journal of Molecular Structure, 2020, vol. 1203]
[10]Nawaz Khan, Fazlur Rahman; Teja, Chitrala [Organic Letters, 2020, vol. 22, # 5, p. 1726 - 1730]
[11]Nesaragi, Aravind R.; Kamble, Ravindra R.; Bayannavar, Praveen K.; Shaikh, Saba Kauser J.; Hoolageri, Swati R.; Kodasi, Barnabas; Joshi, Shrinivas D.; Kumbar, Vijay M. [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 41]
[12]Marganakop; Kamble; Nesaragi; Bayannavar; Joshi; Kattimani; Sudha [Asian Journal of Chemistry, 2021, vol. 33, # 5, p. 1107 - 1114]

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[ 136812-21-0 ]

Reference： [1]Green Chemistry,2018,vol. 20,p. 266 - 273
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2009,vol. 48,p. 152 - 154
[3]Tetrahedron,2011,vol. 67,p. 9219 - 9224

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[ 73568-26-0 ]
[ 1122-41-4 ]
[ 1309388-93-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydride In dimethyl sulfoxide at 90℃; for 3h;	4.2. General procedure for the preparation of 2-arylthioquinoline-3-carbaldehyde 2 General procedure: To a mixture of thiophenol (11 mmol), NaH (20 mmol), and DMSO (20 mL) was added 2-chloro-3-formylquinolines 1 (10 mmol) and the mixture was heated at 90 °C for the given time. Then the reaction was quenched with water (60 mL) and extracted with CH2Cl2 (3×50 mL). The combined organic layer was washed with brine solution, dried over anhydrous Na2SO4, and concentrated in vacuo. The desired products 2 were obtained by flash column chromatography on silica (n-hexane/EtOAc, 10:1→6:1, v/v).

Reference： [1]Location in patent: experimental part Zhong, Weihui; Ma, Wang; Liu, Yanbin [Tetrahedron, 2011, vol. 67, # 19, p. 3509 - 3518]

17
[ 73568-26-0 ]
[ 106-45-6 ]
[ 1309388-94-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium hydride In dimethyl sulfoxide at 90℃; for 2h;	4.2. General procedure for the preparation of 2-arylthioquinoline-3-carbaldehyde 2 General procedure: To a mixture of thiophenol (11 mmol), NaH (20 mmol), and DMSO (20 mL) was added 2-chloro-3-formylquinolines 1 (10 mmol) and the mixture was heated at 90 °C for the given time. Then the reaction was quenched with water (60 mL) and extracted with CH2Cl2 (3×50 mL). The combined organic layer was washed with brine solution, dried over anhydrous Na2SO4, and concentrated in vacuo. The desired products 2 were obtained by flash column chromatography on silica (n-hexane/EtOAc, 10:1→6:1, v/v).

Reference： [1]Location in patent: experimental part Zhong, Weihui; Ma, Wang; Liu, Yanbin [Tetrahedron, 2011, vol. 67, # 19, p. 3509 - 3518]

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[ 79-19-6 ]
[ 104827-57-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	In methanol for 1h; Reflux;
74%	Stage #1: 2-chloro-8-methyl-quinoline-3-carbaldehyde; thiosemicarbazide In ethanol Stage #2: With acetic acid In ethanol at 60℃; for 12h;	4.2. Preparation of 4-Substituted1-((2,8-dichloroquinolin-3-yl)methylene)thiosemicarbazide General procedure: Synthesized thiosemicarbazides (1 equiv.) were dissolved in 10 mL of absolute EtOH, followed by addition of a solution of 2,8-disubstituted quinoline-3-carboxaldehyde (1 equiv.) in EtOH. After stirring for an initial period of 15-30 min, AcOH was added in catalytic amount to increase the yield of the reaction. The mixture was heated to reflux at 60 °C for 12 h. The resultant mixture was evaporated in vacuo to give crude solid products, which were further purified by column chromatography (CH2Cl2/MeOH) to yield compounds 1A-24A.
	In water at 20℃;

Reference： [1]Location in patent: experimental part Desai; Harsora [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 7, p. 1011 - 1019]
[2]Location in patent: experimental part Bhat, Abdul R.; Tazeem; Azam, Amir; Choi, Inho; Athar, Fareeda [European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3158 - 3166]
[3]Marganakop, Sheetal Babu; Kamble, Ravindra Ramappa; Hoskeri, Joy; Prasad, D. Jagadish; Meti, Gangadhar Yamanappa [Medicinal Chemistry Research, 2014, vol. 23, # 6, p. 2727 - 2735]

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[ 104827-61-4 ]