Potassium Acetate → 4-(4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl)[1,2]oxaborolo[4,3-c]pyridin-1(3H)-ol

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Reaction Conditions

Reaction Steps

4-Chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 107e was prepared following the procedures for intermediate 108a in U.S. Pat. No. 8,716,274, Example 108, Figure 8, and from 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one from U.S. Pat. No. 8,729,072, Example 103e. To a solution of 107e (12.0 g, 35.0 mmol) in MeOH (40 mL) and DCM (40 mL) was added NaBH4 (1.83 g, 38.4 mmol) in batches at 0° C. The reaction mixture was stirred at 0° C. for 1 h, quenched with water and concentrated. The residue was partitioned between EA and brine. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude product 4-Chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbinol 107f was used in next step without further purification (9.6 g, 80%). A mixture of compound 107f (9.6 g, 27.8 mmol), tetrahydroxydiborane, hypodiboric acid (7.43 g, 83.5 mmol), Xphos-Pd-G2 (218 mg, 0.278 mmol), Xphos (321 mg, 0.556 mmol) and KOAc (6.85 g, 83.5 mmol) in EtOH (200 mL) was heated to 80° C. for 1 h and concentrated. The residue was dissolved in sat. K2CO3 (100 mL) and extracted with DCM 4 times. The organic phase was discarded and the aqueous layer was neutralized with conc. HCl. White precipitate evolved and the suspension was extracted with DCM. The organic layer was combined, dried over Na2SO4, filtered and concentrated to give 107g as a gray solid (6.21 g, 53%).

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