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Chemical Structure| 1354455-86-9 Chemical Structure| 1354455-86-9

Structure of 1354455-86-9

Chemical Structure| 1354455-86-9

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Product Details of [ 1354455-86-9 ]

CAS No. :1354455-86-9
Formula : C12H13BrN2O
M.W : 281.15
SMILES Code : O=C1N=C(C(C)(C)C)NC2=C1C=CC(Br)=C2
MDL No. :MFCD21607349

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Application In Synthesis of [ 1354455-86-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1354455-86-9 ]

[ 1354455-86-9 ] Synthesis Path-Downstream   1~4

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YieldReaction ConditionsOperation in experiment
84.3% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In methanol; toluene; at 115℃;Inert atmosphere; Microwave irradiation; Sealed tube; Example 1N-{4-[2-tert-Butyl-4-(6-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-quinazolin-7-yl]-phenyl}-methanesulfonamide (I-1; SCHEME A); step 1: To a suspension of 20a (3 g, 14 mmol, CASRN 112253-70-0) in DCM cooled to 0 C. and maintained under a N2 atmosphere was added TEA and the suspension stirred for 15 min. To the suspension was added slowly pivaloyl chloride (1.68 g, 14 mmol) the solution was stirred over night RT. The solution was recooled to 0 C. and a second aliquot of pivaloyl chloride (300 muL) was added and the resulting mixture stirred for 2 h at 0 C. for 2 h then at RT for 2 h. The reaction mixture was concentrated in vacuo to afford 20b which was used without additional purification.step 2: To a suspension of 20b (4.2 g, 14 mmol) and EtOH (28 mL) was added aqueous NaOH (2.8 mL, 28 mmol, 10M solution) and the resulting mixture was heated at reflux under an N2 atmosphere for 1.5 h. The solution was cooled to RT, poured over ice and neutralized with1N HCl. The resulting mixture was twice extracted with EtOAc. The combined extracts were washed with brine, dried (MgSO4), filtered and evaporated to afford 2.07 g of 22a as a yellow solid.step 3: A microwave vial was charged with 22a (0.5 g, 1.78 mmol), 4-methansulfonamido-phenyl boronic acid (0.421 g, 1.96 mmol, CASRN 380430-57-9), Pd(PPh3)4 (0.206 g, 0.178 mmol), Na2CO3 (0.566 g, 5.34 mmol), MeOH (3 mL) and toluene (1.5 mL). The vial was flushed with Ar for 5 min, sealed and irradiated in a microwave synthesizer at 115 C. The reaction mixture was cooled and concentrated. The insoluble material was triturated with Et2O which afford 0.55 g (84.3%) of 22b as a brown solid.step 4: To a suspension of 22b (0.1 g, 0.27 mmol) in benzene (0.5 mL) was added sequentially diethylaniline (73.0 muL, 0.45 mmol) and POCl3 (14.8 muL). The mixture was heated at reflux for 6 h, cooled and diluted with EtOAc. The resulting solution was washed sequentially with 1 N HCl, H2O, satd. aq. NaHCO3, H2O and brine. The solution was dried (MgSO4), filtered and evaporated to afford 24.step 5: A vial was charged with 24 (0.107 g, 0.274 mmol), 6-methyl-2-methoxy-pyridin-3-yl boronic acid (0.055 g, 0.33 mmol), PdC12(dPPf).CH2Cl2 (0.010 g, 0.014 mmol), Cs2CO3 (0.822 g, 0.268 mmol). dioxane (1 mL) and H2O (0.25 mL), purged with Ar for 10 min sealed and heated for 1 h. The solution was cooled to RT, diluted with EtOAc and sequentially extracted with twice with H2O and brine. The resulting solution was dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (10 to 30% EtOAc) to afford 0.08 g of 26.step 6: A mixture of 26 (0.08 g, 0.169 mmol), 48% aq. HBr (52 muL) and HOAc was heated in sealed tube at 60 C. for 3 h. The tube was cooled and the mixture diluted with EtOAc, neutralized with satd. aq. NaHCO3 and stirred overnight at RT. The EtOAc had evaporated and the remaining yellow solid was filtered and washed with EtOAc and H2O. The solid was dried at 70 C. overnight in a vacuum oven which afforded I-1.
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