These common heterocyclic compound, 89830-98-8, name is 5-Cyclopropyl-1H-imidazole, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. SDS of cas: 89830-98-8
To a stirred solution of 9-(2H- 1 ,2,3-triazol-2-y)-3,4,7,8-tetrahydro-[1 ,4]diazepino[7,1-a]isoquinoine-2,5-dione (97 mg, 0.328 mmol) in 1 ,2-dichloroethane (3 mL) was added POCI3 (0.061 mL, 0.657 mmol) at rt and the resulting suspension was stirred at 100¡ãC for 35 min. The reaction mixture was cooled to rt and concentrated under reduced pressure to dryness. For complete removal of POCI3 the residue was taken up in toluene and the solvent was evaporated under reduced pressure. The residue was dried under high vacuo at rt. The resulting crude choro intermediate was dissolved in 1 ,2-dichloroethane (3 ml_), 4- cyclopropyl-1 H-imidazole (107 mg, 0.985 mmol) was added and the mixture was stirred at 100¡ãC for 2h. The reaction mixture was allowed to warm to rt and diluted with DCM. Saturated aqueous NaHC03 solution was added and the mixture was extracted twice with DCM. The combined organic layers were washed with brine, dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: pure DCM for 3 min, then from 0percent MeOH in DCM to 5percent MeOH in DCM in 14 min, 5percent MeOH in DCM for 3 min) to yield a yellow foam. Further purification by SFC (column: 2-Ethylpyridine 5 mutauiota, 250 x 30 mm, 60A, Princeton; eluent: 8percent MeOH/C02 for 1 min, then from 8percent MeOH/C02 to 13percent MeOH/C02 in 6 min ; flow 100 ml_ min ; U V detection at 220 n m) gave the title compound as slightly yellow foam (21 mg). UPLC-MS: MS 386.2 (M+hT); UPLC rt 0.86 min. 1H NMR (400 MHz, DMSO-d6) delta ppm 0.58 – 0.70 (m, 2 H), 0.74 – 0.82 (m, 2 H), 1.74 – 1.86 (m, 1 H), 2.91 (t, J=5.75 Hz, 2 H), 3.75 (t, J=5.&7 Hz, 2 H), 4.25 (s, 2 H), 7.22 (s, 1 H), 7.43 (s, 1 H), 7.54 – 7.63 (m, 1 H), 7.76 (d, J=8.80 Hz, 1 H), 8.10 (s, 1 H), 8.14 – 8.21 (m, 3 H).
The synthetic route of 5-Cyclopropyl-1H-imidazole has been constantly updated, and we look forward to future research findings.
Reference:
Patent; NOVARTIS AG; BEHNKE, Dirk; CARCACHE, David; ERTL, Peter; KOLLER, Manuel; ORAIN, David; WO2014/30128; (2014); A1;,
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