反应详情

温度

0 °C

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%).

1. customquenched with water
2. concentrationconcentrated
3. customThe residue was partitioned between EA and brine
4. customThe organic layer was separated
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe 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%)
9. temperaturewas heated to 80° C. for 1 h
10. concentrationconcentrated
11. dissolutionThe residue was dissolved in sat. K2CO3 (100 mL)
12. extractionextracted with DCM 4 times
13. customWhite precipitate
14. extractionthe suspension was extracted with DCM
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated