Name: 133240-06-9|2-Ethyl-5,7-dimethyl-1H-imidazo[4,5-b]pyridine|98%
Brand: Ambeed
SKU: A733869
Price: 14.0 USD
Availability: InStock
Rating: 96 (30 reviews)

1
[ 50850-16-3 ]
[ 802294-64-0 ]
[ 133240-06-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	With PPA at 100℃; for 5h;
	With PPA at 80 - 90℃;

Reference： [1]Heitsch, Holger; Becker, Reinhard H.A.; Kleemann, Heinz-Werner; Wagner, Adalbert [Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 4, p. 673 - 678]
[2]Mantlo, Nathan B.; Chakravarty, Prasun K.; Ondeyka, Debra L.; Siegl, Peter K. S.; Chang, Raymond S.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 9, p. 2919 - 2922]

2
[ 116636-30-7 ]
[ 123-62-6 ]
[ 133240-06-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With propionic acid; magnesium chloride at 145℃; for 7h;
82%	With propionic acid; magnesium chloride	001 Intermediate 001c: 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine Intermediate 001b (0.224 g, 1.373 mmol) was treated with propionic acid (1.95 mL, 26.1 mmol), propionic anhydride (1.94 mL, 15.10 mmol) and magnesium chloride (0.196 g, 2.059 mmol) as described in /. Med. Chem. 2007, 50, 828. The crude was purified by ISCO (DCM/MeOH, 0-20%) to yield the title compound as a brown oil (0.220 g, 1.130 mmol, 82 % yield). LC-MS (Method A2): 0.42 min, [M + H]+= 176.7; FontWeight="Bold" FontSize="10" H NMR (400 MHz, MeOD) δ ppm 7.05 (s, 1H), 2.98 (q, / = 7.6 Hz, 2H), 2.59 (s, 6H), 1.43 (t, / = 7.7 Hz, 3H).
81%	With propionic acid; magnesium chloride for 8h; Heating;

45%

With propionic acid; magnesium chloride for 16h; Inert atmosphere; Heating;

Synthesis of 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine(35c). A mixture of 5,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (32b) (10 g, 61.3 mmol), propionic acid (87 ml, 1.18 mol),propionic anhydride (88 ml) and MgCl2 (5.83 g, 61.3 mmol) wasstirred overnight at 145 C. Then the mixture was cooled to rt,50 ml of methanol was added followed by 25% ammonia until apH of 9 was reached. The mixture was extracted by ethyl acetate,the organic layers were washed with brine, dried over Na2SO4 andconcentrated. The crude product was purified by MPLC (silica gel,methanol/CH2Cl2, 2-5%). Yield: 4.85 g (45%). 1H NMR (400 MHz,DMSO-d6): d 12.4 (br s, 1H), 6.85 (s, 1H), 2.82 (q, J = 8 Hz, 2H)2.52 (s, 6H), 1.32 (t, J = 8 Hz, 3H); MS (ESI): 176.1 [M+H]+.

Reference： [1]Senanayake, Chris H.; Fredenburgh, Laura E.; Reamer, Robert A.; Liu, Ji; Larsen, Robert D.; Verhoeven, Thomas R.; Reider, Paul J. [Tetrahedron Letters, 1994, vol. 35, # 32, p. 5775 - 5778]
[2]Current Patent Assignee: UNIVERSITY OF MONTREAL; BRISTOL-MYERS SQUIBB CO - WO2018/5591, 2018, A1 Location in patent: Page/Page column 93
[3]Senanayake, Chris H.; Fredenburgh, Laura E.; Reamer, Robert A.; Liu, Ji; Roberts, F. Edward; Humphrey, Guy; Thompson, Andrew S.; Larsen, Robert D.; Verhoeven, Thomas R.; Reider, Paul J.; Shinkai, Ichiro [Heterocycles, 1996, vol. 42, # 2, p. 821 - 830]
[4]Miltz, Wolfgang; Velcicky, Juraj; Dawson, Janet; Littlewood-Evans, Amanda; Ludwig, Marie-Gabrielle; Seuwen, Klaus; Feifel, Roland; Oberhauser, Berndt; Meyer, Arndt; Gabriel, Daniela; Nash, Mark; Loetscher, Pius [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 16, p. 4512 - 4525]

3
[ 133240-06-9 ]
[ 137421-55-7 ]
[ 137421-56-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0℃;

Reference： [1]Dhanoa; Bagley; Chang; Lotti; Chen; Kivlighn; Zingaro; Siegl; Chakravarty; Patchett; Greenlee [Journal of Medicinal Chemistry, 1993, vol. 36, # 23, p. 3738 - 3742]

4
[ 133240-06-9 ]
[ 141281-38-1 ]
[ 151954-41-5 ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 4239 - 4249

5
[ 133240-06-9 ]
[ 100-11-8 ]
[ 137421-60-4 ]

Yield	Reaction Conditions	Operation in experiment
79.1%	Stage #1: 5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine With lithium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-bromomethyl-4-nitro-benzene In N,N-dimethyl-formamide at 20℃; for 0.5h;	7.1 2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (US5424432) (3.50 g, 20.0 mmol) was dissolved in DMF (67 mL), and lithium hydroxide monohydrate (1.26 g, 30.0 mmol) was added thereto, followed by stirring at room temperature for 20 minutes. Then, p-nitorobenzylbromide (4.31 g, 20.0 mmol) was slowly added and stirred at room temperature for 30 minutes. Water (130 mL) was added to the reaction mixture and the precipitated crystals were collected by filtration, followed by washing with water. The crystals was dried under reduced pressure to obtain 2-ethyl-5,7-dimethyl-3-(4-nitrobenzyl)-3H-imidazo[4,5-b]pyridine (4.91 g, 15.8 mmol, yield 79.1%). APCI-MS: m/z 311 [M + H]+ 1H NMR (CDCl3)δ(ppm): 1.32 (t, J = 7.5 Hz, 3H), 2.57 (s, 3H), 2.64 (s, 3H), 2.77 (q, J = 7.5 Hz, 2H), 5.45 (s, 2H), 6.92 (s, 1H), 7.28 (m, 2H), 8.16 (m, 1H).
	With sodium hydride 1.) DMF, RT, 2.) DMF, 6h; Multistep reaction;
	With sodium hydride 1.) DMF, 5 min, 2.) DMF, 2 h; Yield given. Multistep reaction;

Reference： [1]Current Patent Assignee: KIRIN HOLDINGS CO., LTD.; Kyowa Kirin (in: Kirin Holdings) - EP1724271, 2006, A1 Location in patent: Page/Page column 57
[2]Sircar; Winters; Quin III; Lu; Major; Panek [Journal of Medicinal Chemistry, 1993, vol. 36, # 12, p. 1735 - 1745]
[3]Dhanoa, Daljit S.; Bagley, Scott W.; Chang, Raymond S. L.; Lotti, Victor J.; Chen, Tsing-Bau; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 26, p. 4239 - 4249]

6
[ 133240-06-9 ]
[ 138733-52-5 ]
[ 145004-88-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium hydride In N,N-dimethyl-formamide at 50℃; for 3h;

Reference： [1]Chakravarty; Naylor; Chen; Chang; Chen; Faust; Lotti; Kivlighn; Gable; Zingaro; Schorn; Schaffer; Broten; Siegl; Patchett; Greenlee [Journal of Medicinal Chemistry, 1994, vol. 37, # 24, p. 4068 - 4072]

7
[ 133240-06-9 ]
[ 589-15-1 ]
[ 154553-72-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	With 1-methyl-pyrrolidin-2-one; sodium hydroxide for 2h; Ambient temperature;
42%	Stage #1: 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.333333h; Inert atmosphere; Stage #2: 1-bromo-4-(bromomethyl)benzene In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Inert atmosphere;	7.4 4.1.7.4 Synthesis of 3-(4-bromobenzyl)-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (36c) 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (35c) (3 g, 17.1 mmol) was dissolved in 50 ml of DMF. After addition of sodium hydride (60% in mineral oil, 493 mg, 20.5 mmol) in portions, the mixture was stirred for 20 min at rt. 4-Bromobenzylbromide (4.28 g, 17.1 mmol) was added slowly and the mixture was stirred for 2 h at rt. Then the mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated NaHCO3 solution and brine, dried over Na2SO4 and concentrated. The crude product was purified by MPLC (silica gel, ethyl acetate/cyclohexane 2:3) which provided 2.5 g (42%) of the product as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 7.5 (d, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz, 2H), 6.93 (s, 1H), 5.41 (s, 2H), 2.76 (q, J = 8 Hz, 2H), 2.51 (s, 3H), 2.49 (s, 3H), 1.22 (t, J = 8 Hz, 3H); MS (ESI): 344, 346 [M+H]+.
	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;	(a) N-alkylation of imidazoles. General procedure: The appropriate heterocycle (47) (6.0 mmol, 1 equiv.), 4-bromobenzylbromide (6 mmol, 1 equiv.) and base (NaOH for imidazole and NaHfor 2-substituted imidazole) (6 mol, 1 equiv.) in acetonitrile or DMF (10mL) was stirred at ambient temperature overnight. The reaction wasquenched with water (50 mL) and extracted with EtOAc (2 × 50 mL).The combined organic layers were washed with water (30 mL) and brine(25 mL), dried over MgSO4 and concentrated. The crude product waspurified by FCC (50-100% EtOAc in isohexane) to afford theN-alkylated heterocycles in 80-95% yield. 1-(4-bromobenzyl)-2-(tertbutyl)-1H-imidazole 1H NMR (400 MHz, Chloroform-d) δ 7.39 (d, J =8.5 Hz, 2H), 6.90 (d, J = 1.4 Hz, 1H), 6.83 (d, J = 8.6 Hz, 2H), 6.63 (d, J= 1.4 Hz, 1H), 5.20 (d, J = 0.8 Hz, 2H), 1.34 (s, 9H). 13C NMR (101MHz, Chloroform-d) δ 154.5, 136.3, 132.0, 128.0, 126.5, 121.8, 121.7,50.3, 33.5, 29.9. 1-(4-bromobenzyl)-1H-imidazole 1H NMR (400 MHz,Chloroform-d) δ 7.82 (s, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.15 (s, 1H), 7.07(d, J = 8.6 Hz, 2H), 6.92 (s, 1H), 5.15 (s, 2H). 13C NMR (101 MHz,Chloroform-d) δ 137.2, 134.8, 132.3, 129.1, 128.9, 122.5, 119.3, 50.4.

With sodium hydride In N,N-dimethyl-formamide at 20℃; for 12h;

(a) N-alkylation of imidazoles. General procedure: The appropriate heterocycle (47) (6.0 mmol, 1 equiv.), 4-bromobenzylbromide (6 mmol, 1 equiv.) and base (NaOH for imidazole and NaHfor 2-substituted imidazole) (6 mol, 1 equiv.) in acetonitrile or DMF (10mL) was stirred at ambient temperature overnight. The reaction wasquenched with water (50 mL) and extracted with EtOAc (2 × 50 mL).The combined organic layers were washed with water (30 mL) and brine(25 mL), dried over MgSO4 and concentrated. The crude product waspurified by FCC (50-100% EtOAc in isohexane) to afford theN-alkylated heterocycles in 80-95% yield. 1-(4-bromobenzyl)-2-(tertbutyl)-1H-imidazole 1H NMR (400 MHz, Chloroform-d) δ 7.39 (d, J =8.5 Hz, 2H), 6.90 (d, J = 1.4 Hz, 1H), 6.83 (d, J = 8.6 Hz, 2H), 6.63 (d, J= 1.4 Hz, 1H), 5.20 (d, J = 0.8 Hz, 2H), 1.34 (s, 9H). 13C NMR (101MHz, Chloroform-d) δ 154.5, 136.3, 132.0, 128.0, 126.5, 121.8, 121.7,50.3, 33.5, 29.9. 1-(4-bromobenzyl)-1H-imidazole 1H NMR (400 MHz,Chloroform-d) δ 7.82 (s, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.15 (s, 1H), 7.07(d, J = 8.6 Hz, 2H), 6.92 (s, 1H), 5.15 (s, 2H). 13C NMR (101 MHz,Chloroform-d) δ 137.2, 134.8, 132.3, 129.1, 128.9, 122.5, 119.3, 50.4.

Reference： [1]Senanayake, Chris H.; Fredenburgh, Laura E.; Reamer, Robert A.; Liu, Ji; Roberts, F. Edward; Humphrey, Guy; Thompson, Andrew S.; Larsen, Robert D.; Verhoeven, Thomas R.; Reider, Paul J.; Shinkai, Ichiro [Heterocycles, 1996, vol. 42, # 2, p. 821 - 830]
[2]Miltz, Wolfgang; Velcicky, Juraj; Dawson, Janet; Littlewood-Evans, Amanda; Ludwig, Marie-Gabrielle; Seuwen, Klaus; Feifel, Roland; Oberhauser, Berndt; Meyer, Arndt; Gabriel, Daniela; Nash, Mark; Loetscher, Pius [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 16, p. 4512 - 4525]
[3]Gopalan, Greeshma; Hallberg, Mathias; Larhed, Mats; Palo-Nieto, Carlos; Petersen, Nadia N. [Bioorganic and Medicinal Chemistry, 2022, vol. 65]
[4]Gopalan, Greeshma; Hallberg, Mathias; Larhed, Mats; Palo-Nieto, Carlos; Petersen, Nadia N. [Bioorganic and Medicinal Chemistry, 2022, vol. 65]

8
[ 133240-06-9 ]
4'-(bromomethyl)-N-<(dimethylamino)methylene>-(1,1'-biphenyl)-2-sulfonamide [ No CAS ]
4'-(2-Ethyl-5,7-dimethyl-imidazo[4,5-b]pyridin-3-ylmethyl)-biphenyl-2-sulfonic acid 1-dimethylamino-meth-(E)-ylideneamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With caesium carbonate In N,N-dimethyl-formamide for 24h; Ambient temperature;

Reference： [1]Heitsch, Holger; Becker, Reinhard H.A.; Kleemann, Heinz-Werner; Wagner, Adalbert [Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 4, p. 673 - 678]

9
2,6-dimethyl-8-hydroxy-1-deazapurine [ No CAS ]
[ 123-62-6 ]
[ 133240-06-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With propionic acid; magnesium chloride at 120℃; for 16h; microwave irradiation;

Reference： [1]Chang, Lisa C. W.; Von Frijtag Drabbe Künzel, Jacobien K.; Mulder-Krieger, Thea; Westerhout, Joost; Spangenberg, Thomas; Brussee, Johannes; Ijzerman, Adriaan P. [Journal of Medicinal Chemistry, 2007, vol. 50, # 4, p. 828 - 834]

10
[ 89856-44-0 ]
[ 133240-06-9 ]