Category: 53484-17-6

Synthetic Route of 53484-17-6, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 53484-17-6 name is 1-Methyl-1H-benzo[d]imidazole-5-carboxylic acid, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To a stirred solution acid compound 172 (6.7 g, 38.06 mmol) and N,O- dimethylhydroxylamine (5.57 g, 57.09 mmol) in DCM (70 mL) at 0 oC was added DIPEA (13.53 mL, 76.13 mmol), stirred for 15 min, followed by addition of HATU (21.69 g, 57.09 mmol), again stirred for 15 min. The reaction mixture was then stirred at room temperature for overnight. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water and extracted with DCM. The combined organic layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford a crude compound. The crude compound was purified by silica gel column chromatography using 2% MeOH/DCM to afford the title compound 173 (8.1 g, 98.78%) as a brown liquid. TLC: 5% MeOH/DCM (Rf: 0.3). 1H LCMS Calculated for C11H13N3O2: 219.10; LCMS observed: 219.95 (M+1)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Methyl-1H-benzo[d]imidazole-5-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; ASSEMBLY BIOSCIENCES, INC.; TURNER, William, W., Jr.; LI, Leping; HAYDAR, Simon, Nicolas; BURES, Mark, G.; RAI, Roopa; FRANCIS, Samson; ARNOLD, Lee, Daniel; (0 pag.)WO2018/160878; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 53484-17-6,Some common heterocyclic compound, 53484-17-6, name is 1-Methyl-1H-benzo[d]imidazole-5-carboxylic acid, molecular formula is C9H8N2O2, 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.

(4aR,9aS)-2,3,4,4a,9,9a-hexahydro-1Hindeno[2,1-b]pyridine-6-carbonitrile (0.91 g, 4.59 mmol) and 1-methyl-1Hbenzimidazole-5-carboxylic acid (1.02 g, 95.0%, 5.51 mmol, 1.2 Eq) were addedinto a 100-ml round-bottom flask. Anhydrous acetonitrile (5 ml) was added, andstirring was started to obtain a slurry. Triethylamine (2.56 ml, 18.38 mmol, 4.0Eq) was added at room temperature. The reaction mixture was cooled toapproximately 3C and propane phosphonic acid anhydride [3.05 g, 50 wt.% intetrahydrofuran (THF), 4.80 mmol, 1.05 Eq] was added dropwise, keeping theinternal temperature below 11C. The resulting slurry was stirred at roomtemperature and monitored by HPLC and LC-MS for conversion. After 20 hoursat room temperature, the reaction reached approximately 98% conversion. Water(5 ml) was added dropwise, keeping the internal temperature below 35C.Subsequently, a 50% sodium hydroxide aqueous solution (1.84 g, 22.97 mmol,5.0 Eq) was added. The resulting mixture was stirred at room temperature for2 hours. The mixture was extracted with 2-methyl-THF (2 50 ml), and thelayers were separated. The combined organic layers were dried over anhydrousmagnesium sulfate (MgSO4), filtered and concentrated to give a crude oil, which was purified by flash chromatography (100 g silica gel 230-400 mesh) by elutionwith pure ethyl acetate first, and then a solution of 5%-20% methanol in ethylacetate. The fractions containing the desired product were pooled togetherand concentrated under vacuum to give (4aR,9aS)-1-(1-methyl-1H-benzo[d]-imidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile (N-methylbenzimidazole regioisomer 1, M1) as an off-white solid(1.50 g, 91.6% yield). The identity of M1 was confirmed by NMR analysis (1H,13C, correlation spectroscopy, rotating-frame nuclear Overhauser effect correlationspectroscopy, heteronuclear multiple quantum coherence, and heteronuclearmultiple bond coherence) in DMSO-d6 at 80C (Supplemental Figs. 1-6). 1HNMR (CD3SOCD3, 600 MHz, 353 K) d 8.18 (s, 1H), 7.67 (d, J = 1.2 Hz, 1H),7.63 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 7.8 and 1.8 Hz, 1H), 7.41 (d, J= 7.8 Hz, 1H), 7.32 (dd, J = 7.8 and 1.8 Hz, 1H), 4.80 (br, 1H), 4.05 (br, 1H), 3.84(s, 3H), 3.24 (dd, J = 16.2 and 10.8 Hz, 1H), 3.14 (dt, J = 11.4 and 6.6 Hz, 1H),2.95-3.05 (m, 2H), 1.98-2.04 (m, 1H), 1.59-1.65 (m, 1H), 1.47-1.56 (m, 1H),1.28-1.36 (m, 1H). 13C NMR (CD3SOCD3, 150 MHz) d 170.45, 147.16, 145.40,145.29, 142.53, 134.81, 130.34, 129.72, 126.61, 125.67, 120.63, 118.50, 117.31,109.65, 109.05, 54.80, 41.00, 39.50 (br), 32.16, 30.20, 27.24, 22.44. LC-MScalculated for C22H20N4O [M+ H]+: 357.17, Found: 357.20.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-benzo[d]imidazole-5-carboxylic acid, its application will become more common.

Reference:
Article; Maw, Hlaing H; Zeng, Xingzhong; Campbell, Scot; Taub, Mitchell E; Teitelbaum, Aaron M; Drug Metabolism and Disposition; vol. 46; 6; (2018); p. 770 – 778;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem