Name: 30148-21-1|Ethyl 1-methyl-1H-imidazole-2-carboxylate|98%
Brand: Ambeed
SKU: A212275
Price: 7.0 USD
Availability: InStock
Rating: 91 (40 reviews)

1
[ 616-47-7 ]
[ 541-41-3 ]
[ 30148-21-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In acetonitrile; at 0 - 20℃; for 16h;	(Reference Example 9) Synthesis of ethyl 1-methyl-1H-imidazole-2-carboxylate: Triethylamine (3.40 mL, 24.4 mmol) and ethyl chloroformate (2.34 mL, 24.4 mmol) were added to a solution of 1-methyl-1H-imidazole (1.00 g, 12.2 mmol) in acetonitrile (4.0 mL) at 0C and the reaction liquid was stirred at room temperature for 16 hours. The reaction liquid was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate) to obtain ethyl 1-methyl-1H-imidazole-2-carboxylate (1.50 g, 9.73 mmol, 80%) as a white solid. 1H-NMR (400 MHz, CDCl3) delta: 1.42 (3H, t, J=7.2 Hz), 4.01 (3H, s), 4.40 (2H, q, J=7.2 Hz), 7.01-7.03 (1H, m), 7.13-7.15 (1H, m). ESI-MS: m/z= 155 (M+H)+.
80%	With triethylamine; In acetonitrile; at 0 - 20℃; for 16h;	Triethylamine (3.40 mL, 24.4 mmol) and Ethyl chloroformate (2.34 mL, 24.4 mmol) were added at 0 C. to an acetonitrile (4.0 mL) solution of 1-methyl-1H-imidazole (1.00 g, 12.2 mmol), and the reaction solution was stirred at room temperature for 16 hours. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate), thereby obtaining ethyl 1-methyl-1H-imidazole-2-carboxylate (1.50 g, 9.73 mmol, 80%) as a white solid.1H-NMR (400 MHz, CDCl3) delta: 1.42 (3H, t, J=7.2 Hz), 4.01 (3H, s), 4.40 (2H, q, J=7.2 Hz), 7.01-7.03 (1H, m), 7.13-7.15 (1H, m)ESI-MS: m/z=155 (M+H)+
71%	With triethylamine; In acetonitrile; at -20 - 30℃; for 14h;Inert atmosphere; Large scale;	(Comparative Examples 1 to 4) 1-methyl-1H-imidazole 3.3 g scaleAfter replacing the inside of a 100 mL three-necked flask with an argon atmosphere, 22 mL of acetonitrile, 3.3 g of 1-methyl-1H-imidazole and triethylamine in the amounts shown in Table 1 were added and cooled to -20 C. To this solution, a solution of ethyl chloroformate in the amount shown in Table 1 in 8 mL of acetonitrile was added at the addition time shown in Table 1. Thereafter, the mixture was stirred at room temperature for the reaction time shown in Table 1. To the reaction solution were added 20 mL of ethanol and 10 mL of water to dissolve the precipitate, and 1 mL was collected from the homogenized solution. The collected solution was diluted 1000-fold with acetonitrile and subjected to HPLC analysis, and the yield was calculated. The results are shown in Table 2.

68%	With triethylamine; In acetonitrile; at -20 - 20℃; for 3.5h;	To a solution of N-methylimidazole (5 g, 0.06 mol), acetonitrile (32 mL) and triethylamine (15 mL), cooled to-20C was added ethyl CHLOROFORMATE (13 mL, 0.137 mol), and the mixture allowed to slowly warm to room temperature and stirred for 3.5 hr. The solution was filtered (triethylamine hydrochloride) and concentrated under vacuum. The residue was purified by distillation under reduced pressure (0 Torr, 102C) to yield the product as a white solid. Yield (6.26 g, 68%) 1H NMR (DMSO): 8 7.44 (d, 1H, J=2. 8 Hz), 7.04 (d, 1H,. J=2. 8 Hz), 4.26 (q, 2H, J=3. 5 Hz), 3.91 (s, 3H), 1.26 (t, 3h, 7 3. 5 Hz). 13C (DMSO): 159.3, 129.1, 127.7, 61.0, 36.0, 14.5.
66%	With triethylamine; In acetonitrile; at -30 - 20℃;	N-methylimidazole-2-carboxaldehyde Dry acetonitrile (600 ML) was added to N-methylimidazole (150 g, 1.8 mol), followed by triethylamine (503 ML, 3.6 mol) in one portion, and the mixture cooled TO-30 C. Neat ethyl chloroformate (350 mL, 3.6 mol) was added slowly over 15 min. The turbid mixture was then warmed to room temperature and maintained overnight. The solid triethyl ammonium chloride was filtered off, washed with EtOAc, and the filtrate concentrated in vacuo. Dichloromethane (500 ML) was added and the solution was extracted with water (300 mL), the organic phase dried with magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (SIO2, EtOAc) and recrystallization from ether/heptane (2: 1) to provide 188 g (66%) of N-METHYLIMIDAZOLE-2-CARBOXY ethyl ester. This N-methylimidazole-2-carboxy ethyl ester (120 g, 0.77 mol) was treated with a solution of sodium hydroxide (37 g, 0.9 mol) in water (60 mL), and the mixture heated at reflux for 1 h. The mixture cooled to 50 C, acidified to pH 2 with concentrated HC1, cooled further to 5 C and the precipitate filtered. The solid was washed with ether, diluted into water (70 mL), heated gently under 60 C, and upon cooling the product crystallizes to give 75 g (77%) of N-METHYLIMIDAZOLE-2-CARBOXYLIC acid, which was converted into the corresponding aldehyde as described for Intermediate 23.
51%	With triethylamine; In acetonitrile; at -30 - 10℃;	Triethyl amine (5OmL) is added to a solution of methyl imidazol (16.3g, 199mmol) in acetonitrile (10OmL), then it is cooled to -300C. A solution of ethyl chloroformate (3ImL, 328mmol) in acetonitrile (5OmL) is added slowly keeping the temperature bellow 100C. The <n="74"/>reaction mixture is concentrated and diluted in water and extracted with chloroform, dried with MgSO4 anh, filtered and evaporated. Recrystallisation from ether yields l-Methyl-lH-imidazole-2- carboxylic acid ethyl ester as an orange oil (15.5g, 51%).
37%		A literature procedure for the synthesis of the title compound was adopted. 2 A solution of N-methyl-1H-imidazole (280 muL, 290 mg, 3.50 mmol) in anhydrous THF (7 mL) was cooled to -78C and n-BuLi (2.5 M in hexanes, 2.2 mL, 3.60 mmol) was added dropwise by syringe under stirring. The resulting yellow solution was stirred for 30 minutes at -78C where upon chlorotrimethylsilane (465 muL, 399 mg, 3.67 mmol) was added dropwise by syringe; after the addition the resulting reaction mixture was allowed to return to room temperature and the stirring was continued for 1 h. The reaction was then cooled back to -78C, ethylchloroformiate (350 muL, 398 mg, 3.67 mmol) was added and the resulting mixture was allowed to warm up to room temperature and further stirred for 1h. The reaction was quenched with water (1 mL) and the solvents were evaporated under reduced pressure. The obtained crude product was dissolved in dichloromethane (100 mL), washed with water (3 x25 mL) and brine (1 x 25 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with EtOAc as eluent, the chromatographic fractions containing the required compound were collected and concentrated under reduced pressure, affording the title compound 1f as a colorless liquid(152 mg, 37%).
	With triethylamine; In acetonitrile; at -30 - 20℃; for 15h;Inert atmosphere;	A solution of the methylimidazole (3.2 mL, 40.0 mmol) in 30 mL de CH3CN:Et3N (2:1) was cooled to -30 C and quickly added to a previously prepared solution of ethyl chloroformiate (7 mL, 66.0 mmol) in 10 mL of CH3CN. The mixture was stirred for 15h at rt. The solvents were removed under reduced pressure; the crude was re-dissolved in water (20 mL) and extracted with chloroform (3 × 20 mL). The organic fractions were dried and concentrated, and the resulting residue was purified by flash cromatography (aluminum oxide, 90% MeOH) to give 3.72 g of a crude ester residue which was directly used for the next step. A solution of this residue (1.5 g, 9.74 mmol) in 15 mL of aqueous NaOH (1 M) was refluxed for 1 h. The resulting mixture was acidified to pH 2.0 using HCl 10% (aprox.15 mL) and lyophilized. The crude was dissolved in MeOH and concentrated underreduced pressure to give 12 as a slighlty pink solid (1.2 g, 98%).

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146
[2]Patent: EP3263565,2018,A1 .Location in patent: Paragraph 0386; 0387
[3]Patent: US2020/172507,2020,A1 .Location in patent: Paragraph 0118-0121
[4]Patent: JP2017/66077,2017,A .Location in patent: Page/Page column 7; 8; 9; 10; 11
[5]Patent: WO2005/33077,2005,A1 .Location in patent: Page/Page column 53
[6]Patent: WO2004/58763,2004,A1 .Location in patent: Page 43
[7]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[8]Patent: WO2009/24585,2009,A2 .Location in patent: Page/Page column 72-73
[9]Organic and Biomolecular Chemistry,2009,vol. 7,p. 229 - 231
[10]Tetrahedron Letters,2015,vol. 56,p. 3855 - 3857
[11]Journal of the American Chemical Society,1957,vol. 79,p. 4922,4926
[12]Tetrahedron,2013,vol. 69,p. 7847 - 7853

2
[ 30148-21-1 ]
[ 616-47-7 ]
[ 17334-08-6 ]

Reference： [1]Journal of the American Chemical Society,1957,vol. 79,p. 4922,4926

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[ 1003-09-4 ]
[ 30148-21-1 ]
[ 111931-13-6 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

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[ 616-47-7 ]
[ 30148-21-1 ]
[ 62366-40-9 ]

Reference： [1]Australian Journal of Chemistry,1983,vol. 36,p. 415 - 418

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[ 108-85-0 ]
[ 30148-21-1 ]
[ 111931-14-7 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

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[ 30148-21-1 ]
[ 4111-54-0 ]
[ 129378-63-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1990,p. 1645 - 1648

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[ 30148-21-1 ]
[ 103-63-9 ]
[ 111931-15-8 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

9
[ 30148-21-1 ]
[ 333-27-7 ]
2-ethoxycarbonyl-1,3-dimethylimidazolium triflate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 239 - 244

10
[ 30148-21-1 ]
[ 4440-01-1 ]
[ 111931-16-9 ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

11
[ 30148-21-1 ]
[ 20062-51-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	With ammonia; ammonium chloride; In water; at 100℃; for 6h;Sealed flask;	NH4CI (0.15Og, 2.8mmol) is added to a solution of l-methyl-lH-imidazole-2-carboxylic acid ethyl ester (15.5g, lOlmmol) in ammonium hydroxide 35% (112ml_) and the reaction is stirred for 6h at 1000C in a sealed reaction flask. The reaction is cooled to 00C and the solid formed filtered and washed with ice water and ether to give l-methyl-lH-imidazole-2-carboxylic acid amide as brown crystals (6.9g, 55%).

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 239 - 244
[2]Journal of Organic Chemistry,1987,vol. 52,p. 4379 - 4381
[3]Patent: WO2009/24585,2009,A2 .Location in patent: Page/Page column 72-73

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[ 30148-21-1 ]
[ 109012-23-9 ]
[ 109012-22-8 ]
[ 1564-49-4 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 541-41-3 ]
[ 35342-89-3 ]
[ 30148-21-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 239 - 244

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[ 30148-21-1 ]
[ 109012-23-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sulfuric acid; nitric acid; at 0 - 20℃; for 1.5h;Heating / reflux;	IM-1 (1.8 g) was dissolved in concentrated H2S04 (5 mL) and cooled to 0C. Nitric acid (90%, 5 mL) was slowly added and the solution warmed to room temperature and then refluxed at-20C for 1.5 hr. The reaction was quenched by pouring onto ice (50 mL). The resulting blue solution was extracted with DCM, dried over sodium sulphate, and evaporated under vacuum to yield a tanned and oily product. The residue was precipitated with CCL4 : EtOH (1 : 1, 5 mL) to yield the product as white crystals. Yield (1.0543 g, 45%). H NMR (DMSO): 6 8.61 (s, 1H), 4.33 (q, 2H, J=6. 4 Hz), 3.97 (s, 3H), 1.29 (t, 3H, J=6. 0 HZ). 13C (DMSO) : 158.2, 145.4, 135.3, 127.4, 62.2, 37.3, 14.5.
22%	With nitric acid; In sulfuric acid;	Preparation of Ethyl 4-nitro-1-methylimidazole-2-carboxylate (10) Compound (17) was carefully dissolved in 1000 ml of concentrated sulfuric acid cooled to 0 C. 90% nitric acid (1 liter) was slowly added maintaining a temperature of 0 C. The reaction was then refluxed with an efficient condenser (-20 C.) in a well ventilated hood for 50 minutes. The reaction was cooled with an ice bath, and quenched by pouring onto 10 liters of ice. The resulting blue solution was then extracted with 20 liters of dichloromethane and the combined extracts were dried and concentrated in vacuo to yield a tan solid which was recrystallized from 22 liters of 21:1 carbon tetrachloride/ethanol. The resulting white crystals were collected by vacuum filtration to provide pure (10). (103 g, 22% yield). TLC (7:2 benzene/ethyl acetate) Rf 0.5, 1 H NMR (DMSO-d6) delta 8.61 (s, 1 H), 4.33 (1, 2 H, J=6.4 Hz), 3.97 (s, 3 H), 1.29 (t, 3 H, J=6.0 Hz); 13 C NMR (DMSO-d6) delta 158.2, 145.4, 135.3, 127.4, 62.2, 37.3, 14.5; IR(KBr) 3139, 1719, 1541, 1508, 1498, 1381, 1310, 1260, 1147, 1122, 995, 860, 827, 656; FABMS m/e 200.066 (M+H 200.067 calc. for C7 H10 N3 O4).

Reference： [1]Patent: WO2005/33077,2005,A1 .Location in patent: Page/Page column 53-54
[2]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146
[3]Patent: US6090947,2000,A

15
[ 30148-21-1 ]
5-methyl-4-oxo-3-phenyl-4,5-dihydro-3H-imidazo[2,1-f][1,2,4]-8-triazinium-2-olate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536
[2]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

16
[ 30148-21-1 ]
5-methyl-4-oxo-3-phenyl-4,5-dihydro-3H-imidazo[2,1-f][1,2,4]-8-triazinium-2-thiolate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

17
[ 30148-21-1 ]
2-ethoxycarbonyl-3-methylimidazolium N-(N'-benzoyl)amidine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

18
[ 30148-21-1 ]
2,3-diethoxycarbonyl-4-hydroxy-5-methyl-3H-imidazo[1,2-b]-8-pyridazinium inner salt [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

19
[ 30148-21-1 ]
2,3-diethoxycarbonyl-4-hydroxy-1,2-dihydro-5-methyl-3H-imidazo[1,2-b]-8-pyridazinium inner salt [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

20
[ 30148-21-1 ]
4-methyl-3-phenyl-2-phenylcarbamoyloxy-3H,4H-imidazo[1,2-b][1,2,4]triazole-3a-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

21
[ 30148-21-1 ]
5-methyl-4-oxo-3-p-tolyl-2-p-tolylamino-4,5-dihydro-3H-imidazo[2,1-f][1,2,4]-8-triazinium mesitylenesulfonate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 8528 - 8536

22
[ 30148-21-1 ]
[ 128293-62-9 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146

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[ 30148-21-1 ]
[ 180258-48-4 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146

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[ 30148-21-1 ]
[ 195387-60-1 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146

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[ 30148-21-1 ]
[ 180258-47-3 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146

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[ 30148-21-1 ]
[ 195387-59-8 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 6141 - 6146

27
[ 30148-21-1 ]
[ 45515-45-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 239 - 244

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[ 30148-21-1 ]
2-cyano-1,3-dimethylimidazolium triflate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 239 - 244

29
[ 30148-21-1 ]
[ 67319-02-2 ]

Reference： [1]Australian Journal of Chemistry,1983,vol. 36,p. 415 - 418

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[ 30148-21-1 ]
[ 109012-27-3 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-24-0 ]

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[ 30148-21-1 ]
[ 109012-46-6 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
3-(4-amino-1-methyl-5-chlorimidazole-2-carboxamido)propionitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-26-2 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-47-7 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
C₁₀H₁₃N₃O₅ [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-49-9 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 109012-48-8 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-50-2 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-42-2 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-43-3 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-32-0 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[3]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[4]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 109012-31-9 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 109012-41-1 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-40-0 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-30-8 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-51-3 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-36-4 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 104394-09-4 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[3]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[4]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[5]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 104394-08-3 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[3]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[4]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[5]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-37-5 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-44-4 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-45-5 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-38-6 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[3]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[4]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

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[ 30148-21-1 ]
[ 109012-53-5 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[3]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[4]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501
[5]Journal of Organic Chemistry,1987,vol. 52,p. 3493 - 3501

56
[ 30148-21-1 ]
2-(Dicyclohexyl-hydroxy-methyl)-1,3-dimethyl-3H-imidazol-1-ium [ No CAS ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

57
[ 30148-21-1 ]
2-(Hydroxy-di-thiophen-2-yl-methyl)-1,3-dimethyl-3H-imidazol-1-ium [ No CAS ]

Reference： [1]Chemical and pharmaceutical bulletin,1987,vol. 35,p. 1058 - 1069

58
[ 30148-21-1 ]
[ 108418-79-7 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 4379 - 4381

59
[ 30148-21-1 ]
[ 108418-77-5 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 4379 - 4381

60
[ 30148-21-1 ]
[ 108418-78-6 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 4379 - 4381

61
[ 30148-21-1 ]
[ 23356-96-9 ]
[ 1111092-52-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In toluene; at 70℃; for 40h;	Compound (XVIa), which represents a further preferred embodiment of the first aspect of the present invention, was prepared by reacting compound XIV with compound XVa in the presence of a base as follows:

Reference： [1]Patent: WO2013/79942,2013,A1 .Location in patent: Page/Page column 23
[2]Organic and Biomolecular Chemistry,2009,vol. 7,p. 229 - 231
[3]Patent: WO2009/19469,2009,A2 .Location in patent: Page/Page column 26

62
[ 30148-21-1 ]
[ 22348-32-9 ]
[ 1111092-50-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In toluene; at 70℃; for 40h;	Compound (Villa), which represents a preferred embodiment of the first aspect of the present invention, was prepared by reacting compound XII with compound XIIIa in the presence of a base as follows

Reference： [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 229 - 231
[2]Patent: WO2009/19469,2009,A2 .Location in patent: Page/Page column 26
[3]Patent: WO2013/79942,2013,A1 .Location in patent: Page/Page column 20

63
[ 30148-21-1 ]
[ 2026-48-4 ]
[ 1026258-90-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 229 - 231

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[ 30148-21-1 ]
[ 130798-48-0 ]
[ 1117810-86-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 229 - 231

65
[ 30148-21-1 ]
[ 1221722-24-2 ]
[ 20485-43-2 ]

Yield	Reaction Conditions	Operation in experiment
77%		Dry acetonitrile (600 ML) was added to N-methylimidazole (150 g, 1.8 mol), followed by triethylamine (503 ML, 3.6 mol) in one portion, and the mixture cooled TO-30 C. Neat ethyl chloroformate (350 mL, 3.6 mol) was added slowly over 15 min. The turbid mixture was then warmed to room temperature and maintained overnight. The solid triethyl ammonium chloride was filtered off, washed with EtOAc, and the filtrate concentrated in vacuo. Dichloromethane (500 ML) was added and the solution was extracted with water (300 mL), the organic phase dried with magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (SIO2, EtOAc) and recrystallization from ether/heptane (2: 1) to provide 188 g (66%) of N-METHYLIMIDAZOLE-2-CARBOXY ethyl ester. This N-methylimidazole-2-carboxy ethyl ester (120 g, 0.77 mol) was treated with a solution of sodium hydroxide (37 g, 0.9 mol) in water (60 mL), and the mixture heated at reflux for 1 h. The mixture cooled to 50 C, acidified to pH 2 with concentrated HC1, cooled further to 5 C and the precipitate filtered. The solid was washed with ether, diluted into water (70 mL), heated gently under 60 C, and upon cooling the product crystallizes to give 75 g (77%) of N-METHYLIMIDAZOLE-2-CARBOXYLIC acid, which was converted into the corresponding aldehyde as described for Intermediate 23.

Reference： [1]Patent: WO2004/58763,2004,A1 .Location in patent: Page 43

66
[ 30148-21-1 ]
[ 141-78-6 ]
[ 1229426-30-5 ]
[ 141-97-9 ]

Yield	Reaction Conditions	Operation in experiment
66%	With lithium hexamethyldisilazane; In tetrahydrofuran; at -40℃; for 0.333333h;Inert atmosphere;	General procedure: To the solution of ester (10 mmol) in THF (20 mL) and ethyl acetate (70 mmol), LiHMDS (30 mmol) was added very quickly at -40 C, and stirred at this temperature for 20 min. After completion of the reaction, reaction mixture was quenched with acetic acid (50 mmol) and then basified using 10% NaHCO3 solution, extracted with ethyl acetate (2×100 mL), the combined organic layer was washed with water and brine solution and dried over Na2SO4. The specific purification procedure for each compound has been included along with their characterization data.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4193 - 4197

67
[ 616-47-7 ]
[ 109-94-4 ]
[ 30148-21-1 ]

Yield	Reaction Conditions	Operation in experiment
71%		General procedure: n-BuLi (1.67 M solution in hexane, 1.32 mL, 2.2 mmol) was added dropwise into a solution of p-bromochlorobenzene (383 mg, 2.0 mmol) in THF (3 mL) at -78 C for 30 min. Then, ethyl formate (1.6 mL, 20 mmol) was added to the mixture and the obtained mixture was stirred at -78 C. After 3 h at the same temperature, I2 (1523 mg, 6 mmol), K2CO3 (1382 mg, 10 mmol) and EtOH (3 mL) were added at -78 C and the mixture was stirred for 14 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide ethyl 4-chlorobenzoate in 77% yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure ethyl 4-chloro-1-benzoate as a colorless oil.

Reference： [1]Tetrahedron,2012,vol. 68,p. 4701 - 4709

68
[ 30148-21-1 ]
[ 1426429-71-1 ]

Reference： [1]Synlett,2013,vol. 24,p. 215 - 218

69
[ 30148-21-1 ]
[ 23356-96-9 ]
[ 1441046-12-3 ]

Reference： [1]Patent: WO2013/79942,2013,A1

70
[ 30148-21-1 ]
[ 535967-34-1 ]
(S)-[2-(hydroxy-di(m-tolyl)methyl)pyrrolidin-1-yl](1-methyl-imidazol-2-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		(S)-[2-(hydroxydim-tolylmethyl)pyrrolidin-1-yl](1-methyl-imidazol-2-yl)methanone was first prepared by dissolving (S)-a,a-Di(3-methylphenyl)prolinol (prepared as described above, 0.8 g, 2.85 mmol) in toluene (10 mL) and NaH (60 % dispersion in mineral oil, 148 mg,3.7 mmol) added at room temperature. After stirring for 30 mins, ethyl-1-methylimidazole-2-carboxylate (527 mg, 3.4 mmol) was added. The resulting reaction mixture was slowly warm to 70 C and stirred for 24 h at the same temperature. The reaction was cooled to room temperature, quenched by addition of saturated aqueous NH4CI (20 mL) and extracted with dichloromethane (3 x 20 mL). The combined organic extracts were washed with brine (20 mL) and dried over magnesium sulfate. After filtration, the filtrate was evaporated and purified by chromatography on silica gel (10% to 50% ethyl acetate in petroleum ether) to yield the product (0.53 g, 48 %) as white solid; m.p. 162-164C;[a]D-95.5 (c1 .1 in CHCI3);vmax (thin film, cm -1) 2952, 1615, 1456, 1282; deltaEta (500 MHz, d6-DMSO, 100 C) 1 .66-1 .75 (m, 1 H, 1 xCH2), 1 .78-1 .86 (m, 1 H, 1 chi CH2), 1 .93-1 .97 (m, 1 H, 1 chi CH2), 2.05-2.12 (m, 1 H, 1 chi CH2), 2.14 (s, 3H, CH3), 2.29(s, 3H, CH3), 3.36 (s, 3H, NCH3), 3.47-3.52 (m, 1 H, 1 chi CH2), 3.87- 3.92 (m, 1 H, 1 x CH2), 5.68 (s, 1 H, NCH), 6.14 (br, s, 1 H, OH), 6.85-6.87 (m, 2H, ArH), 6.91 - 6.98 (m, 4H, ArH), 7.04 (app. d, 1 H, J 7.7, ArH), 7.18-7.24 (m, 2H, ArH), 7.28 (s, 1 H, ArH); deltaC (126 MHz, d6-DMSO, 100C) 20.6(2 x CH3), 22.2(CH2),27.2 (CH2), 33.6 (CH3),47.4(NCH2), 63.5(NCH), 80.1 (COH), 123.2, 123.3, 123.6, 125.3, 125.9, 126.2, 126.6, 126.9, 127.2, 135.2, 136.1 , 140.2, 145.3, 145.4, 158.9 ( CO) ;mlz (TOF ES+) 390.2188 (100%, MH+, C24H28N3O2 requires 390.2182), 372.2092 (20).

Reference： [1]Patent: WO2013/79942,2013,A1 .Location in patent: Page/Page column 25; 26

71
[ 30148-21-1 ]
[ 22348-32-9 ]
[ 1441045-97-1 ]

Reference： [1]Patent: WO2013/79942,2013,A1

72
[ 30148-21-1 ]
[ 1448855-91-1 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

73
[ 30148-21-1 ]
[ 20485-43-2 ]

Yield	Reaction Conditions	Operation in experiment
98%		A solution of the methylimidazole (3.2 mL, 40.0 mmol) in 30 mL de CH3CN:Et3N (2:1) was cooled to -30 C and quickly added to a previously prepared solution of ethyl chloroformiate (7 mL, 66.0 mmol) in 10 mL of CH3CN. The mixture was stirred for 15h at rt. The solvents were removed under reduced pressure; the crude was re-dissolved in water (20 mL) and extracted with chloroform (3 × 20 mL). The organic fractions were dried and concentrated, and the resulting residue was purified by flash cromatography (aluminum oxide, 90% MeOH) to give 3.72 g of a crude ester residue which was directly used for the next step. A solution of this residue (1.5 g, 9.74 mmol) in 15 mL of aqueous NaOH (1 M) was refluxed for 1 h. The resulting mixture was acidified to pH 2.0 using HCl 10% (aprox.15 mL) and lyophilized. The crude was dissolved in MeOH and concentrated underreduced pressure to give 12 as a slighlty pink solid (1.2 g, 98%).

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

74
[ 30148-21-1 ]
N-[3-(dimethylamine)propyl]-1-methyl-4-[(1-{3-(2-amino-3-mercaptopropanamido)propyl}-4-{1-methyl-1H-imidazole-2-carboxamido}-1H-2-pyrrolyl)carboxamido]-1H-2-pyrrolecarboxamide [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

75
[ 30148-21-1 ]
N-[3-(dimethylamino)propyl]-1-methyl-4-[(4-{1-methyl-1H-imidazole-2-carboxamido}-1H-2-pyrrolyl)carboxamido]-1H-2-pyrrolecarboxamide [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

76
[ 30148-21-1 ]
C₂₉H₄₃N₉O₅ [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

77
[ 30148-21-1 ]
C₂₄H₃₅N₉O₃ [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

78
[ 30148-21-1 ]
C₅₁H₆₂N₁₀O₆S [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 7847 - 7853

79
[ 30148-21-1 ]
[ 107-15-3 ]
N,N'-(ethane-1,2-diyl)bis(1-methyl-1H-imidazole-2-carboxamide) [ No CAS ]

Reference： [1]Journal of Materials Chemistry,2012,vol. 22,p. 8785 - 8792
[2]Inorganica Chimica Acta,2019,vol. 492,p. 268 - 274

80
[ 30148-21-1 ]
[ 95-54-5 ]
N,N'-(1,2-phenylene)bis(1-methyl-1H-imidazole-2-carboxamide) [ No CAS ]

Reference： [1]Journal of Materials Chemistry,2012,vol. 22,p. 8785 - 8792

81
[ 30148-21-1 ]
[ 655-86-7 ]
[Ru(NO)Cl₃(H₂O)_x] [ No CAS ]
[(N,N’-(phenazine-2,3-diyl)-bis(1-methylimidazole-2-carboxamide))Ru(NO)Cl] [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 15554 - 15563

82
[ 30148-21-1 ]
[ 655-86-7 ]
C₂₂H₁₈N₈O₂ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 15554 - 15563

83
[ 30148-21-1 ]
[ 1564-49-4 ]

Yield	Reaction Conditions	Operation in experiment
34.7%	With sulfuric acid; nitric acid; at 70.0℃; for 3h;	Step 6a. A solution of ethyl 1 -methyl- lH-imidazole-2-carboxy late (2.0 g, 13 mmol) in 8 ml cone. H2SO4 and 8 ml cone. HNO3 was stirred for 3 hours at 70C. The solution was diluted with H2O, then adjusted to pH 7-8 with aq Na2C03 solution and extracted with DCM. The organic layer was concentrated and chromatographed (silica, ethyl acetate/petroleum ether) to give the desired compound as yellow solid (0.9g, 34.7%). ESI- MS m/z = 200.20 [M+H]+

Reference： [1]Patent: WO2016/183266,2016,A1 .Location in patent: Page/Page column 50

84
[ 30148-21-1 ]
C₁₇H₁₈F₃N₅O₃ [ No CAS ]

Reference： [1]Patent: WO2016/183266,2016,A1

85
[ 30148-21-1 ]
C₇H₁₁N₃O₂ [ No CAS ]

Reference： [1]Patent: WO2016/183266,2016,A1

86
[ 30148-21-1 ]
C₁₃H₂₀N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2016/183266,2016,A1

87
[ 30148-21-1 ]
C₁₁H₁₆N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2016/183266,2016,A1

88
[ 30148-21-1 ]
[ 92053-25-3 ]
[ 1441046-95-2 ]
(R)-[2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl](1-methyl-1Himidazol-2-yl)methanone [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 2422 - 2435

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	30148-21-1	MDL No. :	MFCD02683326
Formula :	C₇H₁₀N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NOTZYDYZBOBDFE-UHFFFAOYSA-N
M.W :	154.17	Pubchem ID :	4261883
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.43
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	39.58
TPSA :	44.12 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.84 cm/s

Log Po/w (iLOGP) :	1.68
Log Po/w (XLOGP3) :	0.57
Log Po/w (WLOGP) :	0.6
Log Po/w (MLOGP) :	-0.07
Log Po/w (SILICOS-IT) :	0.47
Consensus Log Po/w :	0.65

[ CAS No. 30148-21-1 ] {[proInfo.proName]}

Quality Control of [ 30148-21-1 ]

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Calculated chemistry of [ 30148-21-1 ]

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Medicinal Chemistry

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Application In Synthesis of [ 30148-21-1 ]

[ 30148-21-1 ] Synthesis Path-Upstream 1~10

[ 30148-21-1 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 30148-21-1 ]

Esters

Related Parent Nucleus of
[ 30148-21-1 ]

Imidazoles

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.29
Solubility :	7.85 mg/ml ; 0.0509 mol/l
Class :	Very soluble
Log S (Ali) :	-1.07
Solubility :	13.1 mg/ml ; 0.0853 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.26
Solubility :	8.41 mg/ml ; 0.0546 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.75

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In acetonitrile at 0 - 20℃; for 16 h;	(Reference Example 9) Synthesis of ethyl 1-methyl-1H-imidazole-2-carboxylate: Triethylamine (3.40 mL, 24.4 mmol) and ethyl chloroformate (2.34 mL, 24.4 mmol) were added to a solution of 1-methyl-1H-imidazole (1.00 g, 12.2 mmol) in acetonitrile (4.0 mL) at 0°C and the reaction liquid was stirred at room temperature for 16 hours. The reaction liquid was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate) to obtain ethyl 1-methyl-1H-imidazole-2-carboxylate (1.50 g, 9.73 mmol, 80percent) as a white solid. ¹H-NMR (400 MHz, CDCl₃) δ: 1.42 (3H, t, J=7.2 Hz), 4.01 (3H, s), 4.40 (2H, q, J=7.2 Hz), 7.01-7.03 (1H, m), 7.13-7.15 (1H, m). ESI-MS: m/z= 155 (M+H)⁺.
71%	With triethylamine In acetonitrile at -20 - 30℃; for 14 h; Inert atmosphere; Large scale	(Comparative Examples 1 to 4) 1-methyl-1H-imidazole 3.3 g scaleAfter replacing the inside of a 100 mL three-necked flask with an argon atmosphere, 22 mL of acetonitrile, 3.3 g of 1-methyl-1H-imidazole and triethylamine in the amounts shown in Table 1 were added and cooled to -20 ° C. To this solution, a solution of ethyl chloroformate in the amount shown in Table 1 in 8 mL of acetonitrile was added at the addition time shown in Table 1. Thereafter, the mixture was stirred at room temperature for the reaction time shown in Table 1. To the reaction solution were added 20 mL of ethanol and 10 mL of water to dissolve the precipitate, and 1 mL was collected from the homogenized solution. The collected solution was diluted 1000-fold with acetonitrile and subjected to HPLC analysis, and the yield was calculated. The results are shown in Table 2.
68%	With triethylamine In acetonitrile at -20 - 20℃; for 3.5 h;	To a solution of N-methylimidazole (5 g, 0.06 mol), acetonitrile (32 mL) and triethylamine (15 mL), cooled to-20°C was added ethyl CHLOROFORMATE (13 mL, 0.137 mol), and the mixture allowed to slowly warm to room temperature and stirred for 3.5 hr. The solution was filtered (triethylamine hydrochloride) and concentrated under vacuum. The residue was purified by distillation under reduced pressure (0 Torr, 102°C) to yield the product as a white solid. Yield (6.26 g, 68percent) 1H NMR (DMSO): 8 7.44 (d, 1H, J=2. 8 Hz), 7.04 (d, 1H,. J=2. 8 Hz), 4.26 (q, 2H, J=3. 5 Hz), 3.91 (s, 3H), 1.26 (t, 3h, 7 3. 5 Hz). 13C (DMSO): 159.3, 129.1, 127.7, 61.0, 36.0, 14.5.

66%	With triethylamine In acetonitrile at -30 - 20℃;	N-methylimidazole-2-carboxaldehyde Dry acetonitrile (600 ML) was added to N-methylimidazole (150 g, 1.8 mol), followed by triethylamine (503 ML, 3.6 mol) in one portion, and the mixture cooled TO-30 °C. Neat ethyl chloroformate (350 mL, 3.6 mol) was added slowly over 15 min. The turbid mixture was then warmed to room temperature and maintained overnight. The solid triethyl ammonium chloride was filtered off, washed with EtOAc, and the filtrate concentrated in vacuo. Dichloromethane (500 ML) was added and the solution was extracted with water (300 mL), the organic phase dried with magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (SIO2, EtOAc) and recrystallization from ether/heptane (2: 1) to provide 188 g (66percent) of N-METHYLIMIDAZOLE-2-CARBOXY ethyl ester. This N-methylimidazole-2-carboxy ethyl ester (120 g, 0.77 mol) was treated with a solution of sodium hydroxide (37 g, 0.9 mol) in water (60 mL), and the mixture heated at reflux for 1 h. The mixture cooled to 50 °C, acidified to pH 2 with concentrated HC1, cooled further to 5 °C and the precipitate filtered. The solid was washed with ether, diluted into water (70 mL), heated gently under 60 °C, and upon cooling the product crystallizes to give 75 g (77percent) of N-METHYLIMIDAZOLE-2-CARBOXYLIC acid, which was converted into the corresponding aldehyde as described for Intermediate 23.
51%	With triethylamine In acetonitrile at -30 - 10℃;	Triethyl amine (5OmL) is added to a solution of methyl imidazol (16.3g, 199mmol) in acetonitrile (10OmL), then it is cooled to -30⁰C. A solution of ethyl chloroformate (3ImL, 328mmol) in acetonitrile (5OmL) is added slowly keeping the temperature bellow 10⁰C. The <n="74"/>reaction mixture is concentrated and diluted in water and extracted with chloroform, dried with MgSO₄ anh, filtered and evaporated. Recrystallisation from ether yields l-Methyl-lH-imidazole-2- carboxylic acid ethyl ester as an orange oil (15.5g, 51percent).
37%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h; Inert atmosphere Stage #2: With chloro-trimethyl-silane In tetrahydrofuran; hexane at 20℃; for 1 h; Inert atmosphere Stage #3: at -78 - 20℃; for 1 h; Inert atmosphere	A literature procedure for the synthesis of the title compound was adopted. ² A solution of N-methyl-1H-imidazole (280 μL, 290 mg, 3.50 mmol) in anhydrous THF (7 mL) was cooled to -78°C and n-BuLi (2.5 M in hexanes, 2.2 mL, 3.60 mmol) was added dropwise by syringe under stirring. The resulting yellow solution was stirred for 30 minutes at -78°C where upon chlorotrimethylsilane (465 μL, 399 mg, 3.67 mmol) was added dropwise by syringe; after the addition the resulting reaction mixture was allowed to return to room temperature and the stirring was continued for 1 h. The reaction was then cooled back to -78°C, ethylchloroformiate (350 μL, 398 mg, 3.67 mmol) was added and the resulting mixture was allowed to warm up to room temperature and further stirred for 1h. The reaction was quenched with water (1 mL) and the solvents were evaporated under reduced pressure. The obtained crude product was dissolved in dichloromethane (100 mL), washed with water (3 x25 mL) and brine (1 x 25 mL), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with EtOAc as eluent, the chromatographic fractions containing the required compound were collected and concentrated under reduced pressure, affording the title compound 1f as a colorless liquid(152 mg, 37percent).

Yield	Reaction Conditions	Operation in experiment
45%	at 0 - 20℃; for 1.5 h; Heating / reflux	IM-1 (1.8 g) was dissolved in concentrated H2S04 (5 mL) and cooled to 0°C. Nitric acid (90percent, 5 mL) was slowly added and the solution warmed to room temperature and then refluxed at-20°C for 1.5 hr. The reaction was quenched by pouring onto ice (50 mL). The resulting blue solution was extracted with DCM, dried over sodium sulphate, and evaporated under vacuum to yield a tanned and oily product. The residue was precipitated with CCL4 : EtOH (1 : 1, 5 mL) to yield the product as white crystals. Yield (1.0543 g, 45percent). H NMR (DMSO): 6 8.61 (s, 1H), 4.33 (q, 2H, J=6. 4 Hz), 3.97 (s, 3H), 1.29 (t, 3H, J=6. 0 HZ). 13C (DMSO) : 158.2, 145.4, 135.3, 127.4, 62.2, 37.3, 14.5.
22%	With nitric acid In sulfuric acid	Preparation of Ethyl 4-nitro-1-methylimidazole-2-carboxylate (10) Compound (17) was carefully dissolved in 1000 ml of concentrated sulfuric acid cooled to 0° C. 90percent nitric acid (1 liter) was slowly added maintaining a temperature of 0° C. The reaction was then refluxed with an efficient condenser (-20° C.) in a well ventilated hood for 50 minutes. The reaction was cooled with an ice bath, and quenched by pouring onto 10 liters of ice. The resulting blue solution was then extracted with 20 liters of dichloromethane and the combined extracts were dried and concentrated in vacuo to yield a tan solid which was recrystallized from 22 liters of 21:1 carbon tetrachloride/ethanol. The resulting white crystals were collected by vacuum filtration to provide pure (10). (103 g, 22percent yield). TLC (7:2 benzene/ethyl acetate) Rf 0.5, ¹ H NMR (DMSO-d₆) δ 8.61 (s, 1 H), 4.33 (1, 2 H, J=6.4 Hz), 3.97 (s, 3 H), 1.29 (t, 3 H, J=6.0 Hz); ¹³ C NMR (DMSO-d₆) δ 158.2, 145.4, 135.3, 127.4, 62.2, 37.3, 14.5; IR(KBr) 3139, 1719, 1541, 1508, 1498, 1381, 1310, 1260, 1147, 1122, 995, 860, 827, 656; FABMS m/e 200.066 (M+H 200.067 calc. for C₇ H₁₀ N₃ O₄).

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P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
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P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
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P233	Keep container tightly closed.
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P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
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P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
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P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed

[ CAS No. 30148-21-1 ] {[proInfo.proName]}

Quality Control of [ 30148-21-1 ]

Related Doc. of [ 30148-21-1 ]

Product Details of [ 30148-21-1 ]

Calculated chemistry of [ 30148-21-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 30148-21-1 ]

Application In Synthesis of [ 30148-21-1 ]

[ 30148-21-1 ] Synthesis Path-Upstream 1~10

[ 30148-21-1 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 30148-21-1 ]

Esters

Related Parent Nucleus of [ 30148-21-1 ]

Imidazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 30148-21-1 ]

Related Parent Nucleus of
[ 30148-21-1 ]