反应详情

Prepared using General Procedure 1: A 20 mL microwave vial was charged with 5-(5-bromo-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrile TDZ INT-3 (30 mg, 0.1 mmol), (S)-tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane IND INT-6 (43.6 mg, 0.11 mmol), potassium carbonate (44 mg, 0.32 mmol) and a 3:1 mixture of DME/H2O (2 mL). The reaction mixture was degassed by bubbling N2 gas through the stirring solution for 10 min. Pd(PPh3)4 was added and mixture degassed for additional 2 min. The vial was subjected to microwave irradiation at 100° C. for 40 min. The reaction mixture was cooled to room temperature, diluted with EA (10 mL), and washed with water and brine. The organic layer dried over MgSO4, concentrated, and purified by silica gel chromatography (EA/hexanes) to provide 25 mg (44%) of (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrile as a light yellow solid. LCMS-ESI (m/z) calculated for C24H26FN3OSSi: 451.15; found 452.1 [M+H]+, tR=4.53 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.34-8.25 (m, 2H), 7.85 (d, J=7.6 Hz, 1H), 7.49 (d, J=7.5 Hz, 1H), 7.44-7.34 (m, 2H), 5.34 (t, J=7.1 Hz, 1H), 3.46 (ddd, J=16.8, 9.0, 2.8 Hz, 1H), 3.13 (dt, J=16.8, 8.3 Hz, 1H), 2.61-2.50 (m, 1H), 2.08-1.96 (m, 1H), 0.98-0.95 (m, 9H), 0.22-0.17 (m, 6H).

1. customPrepared
2. customThe reaction mixture was degassed
3. customby bubbling N2 gas through the stirring solution for 10 min
4. additionPd(PPh3)4 was added
5. custommixture degassed for additional 2 min
6. customirradiation at 100° C. for 40 min
7. additiondiluted with EA (10 mL)
8. washwashed with water and brine
9. dry with materialThe organic layer dried over MgSO4
10. concentrationconcentrated
11. custompurified by silica gel chromatography (EA/hexanes)