* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With pyridine In tetrahydrofuran at 65℃; for 3 h; Inert atmosphere
3. Synthesis of intermediate 107-3 Under a nitrogen atmosphere, the intermediate 107-2 (8.0 g, 54.0 mmol) as a raw material was dissolved in 100 mL of anhydrous tetrahydrofuran at room temperature in a 250 mL single-necked flask, followed by sequentially adding carbonyldiimidazole CDI (19.7 g, 108 mmol) and pyridine (8.54 g, 108 mmol) into the reaction system. Next, the reaction system was heated to 65°C, and then carried out for 3h. After detecting the reaction was completed, the reaction system was cooled to room temperature. The reaction mixture was poured into 100 mL of ice water to quench the reaction. The reaction system was washed with 300 mL of dichloromethane three times, and the organic phases were combined, washed with 300 mL of saturated brine three times, dried over anhydrous sodium sulfate and concentrated to dryness. The resulting residue was purified by silica gel column chromatography (eluent: EA/PE (1:10-1:5)), and the product was collected and concentrated to dryness to give 4.2 g of the intermediate 107-3 (45percent) as a white solid. LCMS: 175.1.
Reference:
[1] Patent: EP3216786, 2017, A1, . Location in patent: Paragraph 0553-0554
[2] Journal of Medicinal Chemistry, 1999, vol. 42, # 15, p. 2870 - 2880
[3] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6067 - 6070
[4] Patent: WO2015/65338, 2015, A1, . Location in patent: Page/Page column 49; 50
[5] Patent: WO2015/65336, 2015, A1, . Location in patent: Page/Page column 18
2
[ 57-13-6 ]
[ 118482-03-4 ]
[ 202859-73-2 ]
Reference:
[1] Journal of Medicinal Chemistry, 1997, vol. 40, # 4, p. 586 - 593
[2] European Journal of Medicinal Chemistry, 1997, vol. 32, # 11, p. 843 - 868
1-cyclopropyl-N-ethyl-1H-benzo[d]imidazol-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
In isopropyl alcohol; at 80℃; for 0.25h;Microwave irradiation;
General procedure: A mixture of o-phenylenediamine (1.0 mmol) and EDC.HCl (1.1 mmol) in 2-propanol (10 mL) was irradiated in microwave apparatus at 200 W (80 C) for 15 min. The reaction was monitored by TLC (eluent CH2Cl2 / MeOH 95:5). After completion, the reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2 x 25 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure and the obtained crude product was purified by flash column chromatography using silica gel (100-200 mesh) with 1-5% MeOH/CH2Cl2 as eluent. The fractions containing product were collected and concentrated under reduced pressure to afford N-ethyl-1Hbenzo[d]imidazol-2-amine (1a, 90% yield) as an off white solid.