Application of 61367-07-5, A common heterocyclic compound, 61367-07-5, name is Methyl trans-4-aminocyclohexanecarboxylate hydrochloride, molecular formula is C8H16ClNO2, 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.
Application of 61367-07-5, A common heterocyclic compound, 61367-07-5, name is Methyl trans-4-aminocyclohexanecarboxylate hydrochloride, molecular formula is C8H16ClNO2, 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.
To a suspension of 6-chloro-8-(cyclopropylamino)-N-(3-fluoropyridin-4- yl)imidazo[l,2-b]pyridazine-3-carboxamide (0.030 g, 0.087 mmol) and DIEA (0.227 mL, 1.298 mmol) in NMP (1 mL) was added trans-methyl 4- aminocyclohexanecarboxylate, HCl (0.201 g, 1.038 mmol). The resulting suspension was heated to 120 0C in a 300W CEM Discover microwave for 60 min. The crude material was diluted with 1 mL MeOH and purified via preparatory HPLC using a YMC ODS C-18 column (30 x 250 mm) 0%-100%B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B = O, final % B = 100, gradient time 240 min, hold at 100% B 40 min, flow rate 25 mL/min. Material was redissolved in DMSO/THF and purified via preparatory HPLC using a YMC ODS C-18 column (30 x 250 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B = O, final % B = 100, gradient time 60 min, flow rate 25 mL/min, to afford methyl trans-4-((8-(cyclopropylamino)-3-((3-fluoro-4- pyridinyl)carbamoyl)imidazo[l,2-b]pyridazin-6-yl)amino)cyclohexanecarboxylate, 2TFA (0.006 g, 9.97% yield) obtained as a white foam. LC/MS, m/z 468.0 (M+l). HPLC Rt = 4.120 min. YMC S5 ODS-A column (4.6 x 50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.2% H3PO4). Solvent A: (10% MeOH, 90% H2O, 0.2% H3PO4). Gradient, start % B = O, final % B = 100, gradient time 4 min, hold at 100% 1 min, flow rate 4 mL/min. 1H NMR (500 MHz, DMSO-d6) delta ppm11.46 (1 H, s), 8.67 (1 H, d, J=2.75 Hz), 8.55 (1 H, t, J=5.91 Hz), 8.41 (1 H, d, J=5.77 Hz), 8.00 (1 H, s), 7.57 (1 H, s), 7.00 (1 H, s), 6.07 (1 H, s), 2.06 (3 H, s), 1.91 (4 H, s), 1.58 (1 H, d), 1.30 (4 H, d, J=10.45 Hz), 1.05 (2 H, d, J=I 1.27 Hz), 0.76 (2 H, d, J=4.95 Hz), 0.57 – 0.67 (2 H, m).
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/100375; (2009); A1;,
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