Research on new synthetic routes about

Electric Literature of 149520-94-5, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 149520-94-5, name is Ethyl 2-amino-1H-imidazole-5-carboxylate belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Ethyl 2-amino-1H-imidazole-4-carboxylate (980 mg, 6.8 mmol) and tert- butyl 2-(2,4-dichloroben2ylidene)-3-oxobutanoate (2.03 g, 6.4 mmol) were dissolved in ethanol (15 mL) and the reaction was heated to 75 C for 16 h. The reaction was concentrated under reduced pressure to obtain a 10: 1 mixture (by EtaPLC) of 6-tert- butyl 2-ethyl 5-(2,4-dichlorophenyl)-7-methyl-5,8-dihydroimidazo[1,2-a]pyrimidine- 2,6-dicarboxylate and 6-tert~butyl 3-ethyl 5-(2,4-dichlorophenyl)-7-methyl-5,8- dihydroimidazo[1,2-a]pyrimidine-3,6-dicarboxylate (3.07 g, 100% crude yield) as a yellow foam. A small amount of this mixture (350 mg) was purified by silica gel chromatography to obtain 6-tert-butyl 2-ethyl 5-(2,4-dichlorophenyl)-7-methyl-5,8- dihydroimidazo[1,2-a]pyrimidine-2,6-dicarboxylate (190 mg, 54%) and 6-tert-butyl 3-ethyl 5-(2,4-dichlorophenyl)-7-methyl-5,8-diliydroimidazo[1,2-a]pyrimidine-3 ,6- dicarboxylate (19 mg, 5.4%) as white solids.[00249] For 2-isomer: 1H NMR (400 MHz, CDCl3) delta 10.19 (br s, 1H), 7.43 (d, J= 2.2 Hz, IH), 7.38 (s, 1H), 7.34 (d, J= 7.2 Hz, 1H), 7.21 (dd, J= 2.2, 7.2 Hz, 1H), 6.67 (s, 1H), 4.29 (m, 2H), 2.57 (s, 3H), 1.34 (t, J= 7.0 Hz, 3H), 1.26 (s, 9H).[00250] HPLC-MS Phenomenex LUNA C- 18 4.6 X 50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 4.13 rnin, 98% homogeneity index. [00251] LCMS: Anal. Calcd. for C21H23Cl2N3O4451.11 found: 452.24 (M+H)+. [00252] For 3-isomer: 1H NMR (400 MHz, CDCl3) delta 11.72 (br s, 1H), 7.59 (d, J= 8.4 Hz, 1H), 7.50 (br s, 1H), 7.27 (d, J= 3.5 Hz, 1H), 7.18 (dd, J= 3.0, 8.4 Hz, 1H), 6.91 (s, 1H), 4.16 (m, 2H), 2.44 (s, 3H), 1.41 (s, 9H), 1.26 (t, J= 7.0 Hz, 3H). [00253] HPLC-MS Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 4.24 min, 99% homogeneity index.[00254] LCMS: Anal. Calcd. for C21H23Cl2N3O4451.11 found: 452.24 (M+H)+. [00255] To a stirred solution of 6-tert-butyl 2-ethyl 5-(2,4-dichlorophenyl)-7- methyl-5,8-dmydroimidazo[1,2-a]pyrimidrne-2,6-dicarboxylate (191 mg, 0.42 mmol) in acetone (5 mL) was added KMnO4 (66 mg, 0.42 mmol). After 1 h, the reaction was filtered through celite and concentrated under reduced pressure. The resulting residue was diluted with CH2Cl2 and extracted with H2O (2x). The organic layer was dried EPO over MgSO4, concentrated under reduced pressure and recrystallized from EtOAc to obtain 6-tert-butyl 2-ethyl 5-(2,4-dicMorophenyl)-7-methylimidazo[1,2-a]pyrimidirie- 2,6-dicarboxylate (107 mg, 57%) as white crystals.[00256] To a stirred solution of 6-tert-butyl 3 -ethyl 5-(2,4-dichlorophenyl)-7- methyl-5,8-dihydroimidazo[l ,2-alpha]pyrimidine-3,6-dicarboxylate (19 mg, 0.04 mmol) in acetone (2 mL) was added KMnO4 (7 mg, 0.04 mmol). After 1 h, the reaction was filtered through celite and concentrated under reduced pressure. The resulting residue was diluted with CH2Cl2 and extracted with H2O (2x). The organic layer was dried over MgSO4, concentrated under reduced pressure and purified by silica gel chromatography to obtain 6-tert-butyl 3-ethyl 5-(2,4-dichlorophenyl)-7- methylimidazo[1,2-a]pyrimidine-2,6-dicarboxylate (14 mg, 74%) as white solid. [00257] For 2-isomer: 1H NMR (400 MHz, CDCl3) delta 7.68 (d, J= 1.8 Hz, 1H), 7.53 (s, 1H), 7.50 (dd, J= 1.8, 7.6 Hz, 1H), 7.35 (d, J= 7.6 Hz, 1H), 4.43 (m, 2H), 2.77 (s, 3H), 1.41 (t, J= 7.2 Hz, 3H), 1.29 (s, 9H). [00258] 13C NMR (500 MHz, CDCl3) 6 163.7, 162.7, 159.8, 147.0, 141.1, 138.5, 138.2, 134.5, 131.4, 130.3, 128.1, 127.8, 119.0, 114.1, 83.8, 61.4, 27.7, 24.3, 14.3. [00259] HPLC-MS Phenomenex LUNA C-18 4.6 X 50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 3.89 min, 99% homogeneity index. [00260] LCMS: Anal. Calcd. for C21H21Cl2N3O4449.09 found: 450.11 (M+H)+. [00261] HRMS: Anal. Calcd. for C21H22Cl2N3O4 450.0987 found: 450.0981 (M+H)+.[00262] For 3-isomer: 1H NMR (400 MHz, CDCl3) delta 8.38 (s, 1H), 7.41 (d, J= 1.7 Hz, 1H), 7.41 (m, 2H), 3.98-4.17 (m, 2H), 2.77 (s, 3H), 1.27 (s, 9H), 1.22 (t, J= 7.0 Hz, 3H).[00263] 13C NMR (400 MHz, CDCl3) delta 164.0, 159.1, 158.3, 150.5, 144.4, 142.4, 137.0, 134.8, 131.7, 129.9, 128.9, 126.9, 121.1, 117.6, 83.9, 61.0, 27.5, 23.5, 14.3. [00264] HPLC-MS Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 3.89 min, 99% homogeneity index.[00265] LCMS: Anal. Calcd. for C21H21Cl2N3O4449.09 found: 450.20 (M+H)+. EPO [00266] The regiochemistry for the 2- and 3-isomers were unequivocally established by single crystal X-ray analysis for both compounds.

The synthetic route of Ethyl 2-amino-1H-imidazole-5-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2006/71752; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem