Triethylamine → HCID 90042394, Verbindung

Temperatur

85 °C

In a sealed vial 4,6-dibromobenzo[c][1,2,5]oxadiazole (2.2 g, 8 mmol) was combined with, (888 mg, 8.8 mmol), Et3N (3.3 mL, 24 mmol), and NMP (13 mL). The mixture was heated to 85° C. for 2 days. At this time the reaction was diluted with 1 M NaOH (150 mL) and the insoluble material was removed by filtration. The desired compound was precipitated by the addition of HCl (conc.) to the aqueous layer and isolated by vacuum filtration to give 1-(6-bromobenzo[c][1,2,5]oxadiazol-4-yl)azetidine-3-carboxylic acid (1.7 g), which was used without further purification. The acid (1.5 g, 5 mmol) was dissolved in THF (50 mL) and cooled to 0° C. To this was added BH3-THF (10 mL, 10 mmol). The reaction was allowed to come to room temperature overnight. The next day the reaction was quenched with AcOH and extracted into EtOAc. The organic layer was washed with 1 M NaOH until the washings remained litmus blue and then concentrated in vacuo. The crude material was fused to SiO2 and purified by flash column chromatography (3:2 Hex:EtOAc) to give 800 mg of (1-(6-bromobenzo[c][1,2,5]oxadiazol-4-yl)azetidin-3-yl)methanol (56% yield). 1H NMR (500 MHz, CDCl3) δ=7.05 (s, 1H), 6.11 (s, 1H), 5.30 (s, 1H), 4.11 (t, J=8 Hz, 2H), 3.85 (m, 4H), 3.00 (m, 1H). To a solution of the afore mentioned alcohol (400 mg, 1.4 mmol) in DME (7 mL)/Na2CO3 (2.1 mL) was added 3-formyl-phenylboronic acid (315 mg, 2.1 mmol) and Pd(P(Ph)3)4 (50 mg). The flask was then fitted with a reflux condenser, purged with argon and heated to 115° C. O/N. The reaction was worked up by pouring into 1 M NaOH (150 mL) and isolating the resultant solids by vacuum filtration. The crude material was purified by plugging through SiO2 (50% EtOAc in Hex) to give 350 mg of material which was used as is. To a stirring solution of aldehyde (400 mg, 1.4 mmol) and Rupert's reagent (483 mg, 3.3 mmol) in DCM (13 mL) at 0° C. was added TBAF (0.1 mL, 1 M THF, 0.2 mmol). After 30 min at low temperature the cold bath was removed and the reaction was allowed to come to RT. After stirring overnight an excess of TBAF was added and the reaction was diluted with DCM. The organic phases were washed with saturated NH4Cl, brine, and then dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (30% EtOAc in Hex) to give 150 mg (34% yield). 1H NMR (500 MHz, CDCl3) δ=7.72-7.66 (m, 2H), 7.5 (m, 2H), 7.14 (s, 1H0, 6.04 (s, 1H), 5.11 (m, 1H), 4.41 (t, J=8 Hz, 2H), 4.15 (dd, 2H), 3.93 (d, J=5 Hz, 2H), 3.06 1H), 2.82 (s, broad), 1.63 (s, broad).