Methyl iodide → 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole

Temperatur

0 °C

NaH (1.707 g, 42.68 mmol, 40% dispersion in mineral oil) was added in small portions to a cooled (0° C.) mixture of 3-(2-chloropyrimidin-4-yl)-1H-indole (Intermediate 131, 8.168 g, 35.57 mmol) in THF (250 mL). The resulting mixture was stirred at 0° C. for 0.5 h and then CH3I (2.67 mL, 42.68 mmol) was added and the mixture stirred at 0° C. for a further 3 h. The reaction was quenched by the addition of sat. NaHCO3 (25 mL). The mixture was then diluted with EtOAc (100 mL), and the resulting solution was washed with sat. NaHCO3 (50 mL), water (50 mL) and sat. brine (50 mL). The organic solution was then concentrated in vacuo. Purification by FCC, eluting with 0-20% CH3OH in CH2Cl2 gave the title compound (8.35 g, 96%) as a pale yellow solid; 1H NMR: 3.90 (3H, s), 7.30 (2H, pd), 7.54-7.60 (1H, m), 7.82 (1H, d), 8.38-8.44 (1H, m), 8.49 (1H, s), 8.53 (1H, d); m/z: ES+ MH+ 1244.

1. temperaturea cooled
2. stirringthe mixture stirred at 0° C. for a further 3 h
3. customThe reaction was quenched by the addition of sat. NaHCO3 (25 mL)
4. additionThe mixture was then diluted with EtOAc (100 mL)
5. washthe resulting solution was washed with sat. NaHCO3 (50 mL), water (50 mL) and sat. brine (50 mL)
6. concentrationThe organic solution was then concentrated in vacuo
7. customPurification by FCC
8. washeluting with 0-20% CH3OH in CH2Cl2

ORD-Eintrag

ord-d90bfd57b53647918afe921369fe4374

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08946235B2