Application of 230301-11-8 , The common heterocyclic compound, 230301-11-8, name is tert-Butyl 6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate, molecular formula is C11H17N3O2, 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.
Step 209.2: To a solution of 1,4,6,7-tetrahydro-imidazo[4,5-c]pyridine-5-carboxylic acid tert- butyl ester (279mg) in MeCN (10ml) was added Cs2CO3 (407mg) followed by benzyl bromoacetate (0.2ml). The resulting white suspension was stirred at RT for 48h, diluted with EA and washed with water and brine. The aq. phases were extracted with EA. The combined org. layers were dried (MgS04), filtered off and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 25g cartridge, DCM/MeOH 97/3 for 10CV) to afford 371 mg of oil. The oil was purified by preparative chiral HPLC (I) to afford the two regioisomers, both as mixture of benzyl and ethyl ester that formed during the evaporation of the fractions after HPLC purification: Step 209.3: The Boc protecting group of 1-benzyloxycarbonylmethyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridine-5-carboxylic acid tert-butyl ester was cleaved using a method analogous to that of Example 16 step 16.4 to give (4,5,6,7-tetrahydro-imidazo[4,5-c]pyridin-1-yl)-acetic acid benzyl ester. Step 209.4: To a solution of (4,5,6,7-tetrahydro-imidazo[4,5-c]pyridin-1-yl)-acetic acid benzyl ester (176mg) in MeOH was added formaldehyde (36.5% in water, 0.052ml_) followed by NaBH3CN (29mg) and AcOH (0.5ml_). The reaction mixture was stirred at RT overnight. DCM was added and the mixture was washed with sat. NaHCO3. The aq. layer was extracted with DCM, the combined org. layers were dried (MgS04), filtered off and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 10g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in %B: 25 for 3CV, 25 to 50 over 2CV, 50 for 5CV, 50 to 100 over 3CV, 100 for 2CV) to afford (5-methyl-4,5,6,7-tetrahydro-imidazo[4,5-c]pyridin-1-yl)-acetic acid benzyl ester (39mg, yellow oil). (5-Methyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-2-yl)-acetic acid benzyl ester (1 1 1 mg, colourless oil). LC-MS (B): tR = 0.54min; [M+H]+: 286.16. 1H-NMR (CDCl3): 7.40-7.33 (m, 5H); 7.18 (s, 1 H); 5.21 (s, 2H); 4.89 (s, 2H); 3.50 (s, 2H); 2.86 (t, 2H, 6.0Hz); 2.76 (t, 2H, 5.5Hz); 2.49 (s, 3H). Roesy signal seen between CH2 at 4.89ppm and CH at 7.18ppm. (5-Methyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1 -yl)-acetic acid benzyl ester (45mg, pale yellow solid). LC-MS (B): tR = 0.54min; [M+H]+: 286.16. 1H-NMR (CDCl3): 7.40-7.33 (m, 6H); 5.21 (s, 2H); 4.85 (s, 2H); 3.47 (s, 2H); 2.75 (t, 2H, 6.0Hz); 2.67 (t, 2H, 5.5Hz); 2.49 (s, 3H). Roesy signal seen between CH2 at 4.85ppm and CH2 at 2.67ppm. Step 215.2: The final compound was prepared using a method analogous to that of Example 14 step 14.2, (5-methyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-2-yl)-acetic acid benzyl ester replacing intermediate 14.1 and using MeOH instead of MeOH/AcOH. LC-MS (B): tR = 0.17min; [M+H]+: 196.29.
The synthetic route of 230301-11-8 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ACTELION PHARMACEUTICALS LTD; CAROFF, Eva; KELLER, Marcel; KIMMERLIN, Thierry; MEYER, Emmanuel; WO2013/114332; (2013); A1;,
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