According to the analysis of related databases, 15783-48-9, the application of this compound in the production field has become more and more popular.
Related Products of 15783-48-9, The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 15783-48-9, name is 2,4-Dichlorofuro[3,4-d]pyrimidin-7(5H)-one. This compound has unique chemical properties. The synthetic route is as follows.
2,6-Dihydroxypyrimidine-4-carboxylic acid (100 g, 73.4 mmol) and paraformaldehyde (84 g, 293 mmol) were combined with concentrated HCl (1.5L) and heated to reflux at 85-95 C for 18 hours. The reaction was then cooled and HCl was evaporated under reduced pressure to obtain a solid. The solid was washed with petrolium ether to give crude 2,4-dihydroxyfuro[3,4- d]pyrimidin-7(5H)-one (90 g, 83 % yield) which was used next tep without further purification.[0113] A mixture of 2,4-dihydroxyfuro[3,4-d]pyrimidin-7(5H)-one (lOOg, 595mmol), phosphoryl trichloride (800mL) and N,N-diethylaniline (150 mL) was heated at 110 C for 18 hours. The reaction was cooled to ambient temperature, the solvent was removed in vacuo to give a residue. The residue was purified on a silica gel column eluted with petroliumether_EtOAc=5: l to give 2,4-dichlorofuro[3,4-d]pyrimidin-7(5H)-one (70 g, 57 % yield) as an off-white solid.[0114] A solution of 2,4-dichlorofuro[3,4-d]pyrimidin-7(5H)-one (34g, 165mmol) in DCM (770 mL) was added 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (24 g, 165 mmol) was cooled to 0 C and then triethylamine (96 mL, 660mmol) was added dropwise. The mixture was then concentrated in vacuo to give a residue which was purified on a silica gel column eluted with DCM_EtOAc=l :2 to give 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-chlorofuro[3,4-d]pyrimidin- 7(5H)-one (28 g, 82% yield) as a yellow solid. MS [M+H] found 282.[0115] Under a nitrogen at 0 titanium chloride triisopropoxide (1 M in hexanes) (75 ml, 75 mmol) was added to a solution of 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-chlorofuro[3,4- d]pyrimidin-7(5H)-one (19 g, 68 mmol) in THF (100 mL) followed by dropwise addition of ethylmagnesium bromide (1 M in THF) (150 ml, 150 mmol). The reaction was warmed up to ambient temperature and stirred overnight and then quenched by addition of a saturated NH4C1 solution (200 mL). The water layer was extracted with ethyl acetate, and the combined organic layers were dried over Na2S04, filtered, and evaporated in vacuo to give a residue. The residue was purified on a silica gel column eluted with petrolium ether_EtOAc=3: l to give l-(6-(8-oxa- 3-azabicyclo[3.2.1 ]octan-3-yl)-2-chloro-5-(hydroxymethyl)pyrimidin-4-yl)cyclopropanol (5 g, 24% yield) as a yellow solid. MS [M+H] found 312.[0116] To a solution of l-(6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-chloro-5- (hydroxymethyl)pyrimidin-4-yl)cyclopropanol (3 g, 9.6 mmol) and PPh3(2.5 g,14.4 mmol) in dry THF (200 mL) was added DEAD (3.77 g,14.4 mmol) dropwise at 0 C. The mixture was stirred at ambient temperature for 3 hours. The solvent was removed in vacuum to give a residue which was purified on silica gel column eluted with petroleum ether_EtOAc=4: l to give a residue which was further purified by Prep HPLC (Column: Fuji CI 8 (300×25); Wavelength 220 nm; Mobile phase: A MeCN (0.1% TFA); B water (0.1% TFA); Flow rate: 25 mL /min; Injection volume: 2 mL; Run time: 20 min; Equilibration: 3 min) to give 4′-(8-oxa-3- azabicyclo[3.2.1 ]octan-3-yl)-2′-chloro-5’H-spiro[cyclopropane- 1 ,7′-furo[3,4-d]pyrimidine] (330mg, 12% yield). MS [M+H] found 294.[0117] A mixture of 4′-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2′-chloro-5’H-spiro[cyclopropane- l,7*-furo[3,4-d]pyrimidine] (10.2 mg, 0.035 mmol), l-Methyl-3-[4-(4,4,5,5-Tetramethyl-l,3,2- dioxaborolane-2-yl)phenyl]-urea (19.18 mg, 0.069 mmol), sat. NaHC03 aq. (0.25 ml, 0.035 mmol) and PdCl2(dppf)-CH2Cl2 (2.269 mg, 2.78 muiotaetaomicron) in 1 ,4-Dioxane (0.5 ml) was heated by microwave at 110 C for 30 min. The mixture was passed throught filter and washed with MeOH. The filtrate was purified by preparative HPLC (gradient 20-45% ACN (containing 0.035% TFA) in water (containing 0.05% TFA). The fractions containing the desired compound were combined and concentrated in vacuo to give a solid. This solid was partitioned between EtOAc and NaHC03 aq. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with saturated aqueous NaCl, dried and concentrated in vacuo to give a beige solid, which was triturated with hexane/ethyl acetate (1 : 1), collected by filtration, rinsed with hexane/ethyl acetate (1 :1) and dried to give the title compound (10.1 mg, 0.025 mmol, 71.4 % yield) as a beige solid. 1H NMR (400 MHz, DMSO- 6) delta ppm 1.09 (m, 2 H) 1.18 (m, 2 H) 1.78 (m, 4 H) 2.65 (s, 3 H) 3.25 (m, 2 H) 3.95 (m, 2 H) 4.43 (m, 2 H) 5.32 (s, 2 H) 6.12 (br s, 1 H) 7.47 (d, J=8 Hz, 2 H) 8.14 (d, J= 8 Hz, 2 H) 8.81 (s, 1 H). MS [M+H] found 408.
According to the analysis of related databases, 15783-48-9, the application of this compound in the production field has become more and more popular.
Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; JIN, Bohan; LARDY, Matthew; ZHOU, Feng; DONG, Qing; WO2012/99581; (2012); A1;,
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