Bromide ion → 1H-Indazole

Temperature

135 °C

A mixture of bromide (IXb-75) (120 mg, 0.24 mmol), N,N-dicyclohexylmethylamine (52 mg, 0.27 mmol), 4-(tributylstannyl)thiazole (138 mg, 0.37 mmol), dihydrogen dichlorobis(di-tert-butylphosphinito-kP)palladate(2-) (7 mg, 0.01 mmol) in DMF (3 mL) was stirred at 135° C. for 19 h. The mixture was then cooled to RT and partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with EtOAc (2×15 mL). The combined organic solutions were dried (MgSO4), filtered and concentrated. The orange residue was purified by LCMS (column LUNA 10μ C18(2) 00G-4253-V0 250×50 mm) using water-acetonitrile (0.1% AcOH) as eluent (in gradient; flow 80 mL/min) to afford azaindole (I-116) (24.1 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 1.51-1.67 (m, 4H), 2.03-2.16 (m, 6H), 2.57-2.64 (m, 1H), 3.04-3.12 (m, 5H), 3.82 (t, J=6.0 Hz, 2H), 3.84-3.87 (m, 2H), 6.44 (d, J=3.4 Hz, 1H), 7.31 (d, J=3.4 Hz, 1H), 7.80 (d, J=1.9 Hz, 1H), 8.01 (s, 1H), 8.05 (d, J=1.9 Hz, 1H), 10.29 (br s, 1H).

1. temperatureThe mixture was then cooled to RT
2. custompartitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 solution (10 mL)
3. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
4. dry with materialThe combined organic solutions were dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe orange residue was purified by LCMS (column LUNA 10μ C18(2) 00G-4253-V0 250×50 mm)

ORD record

ord-b1a3b3f917d34ddb828b44e305c7f493

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07951802B2