Sodium Carbonate → 2,5-Dichloro-4-(7-methoxybenzo[b]thiophen-2-yl)-pyrimidine

Temperatur

-78 °C

n-Butyl lithium (4.19 mL, 1.6 M in hexane) is added dropwise over 1 hour to a stirred solution of 7-methoxy-benzo[b]thiophene (1.00 g, 6.09 mmol) and triisopropyl borate (1.26 g, 6.70 mmol) in anhydrous THF (10 mL) at −78° C. under nitrogen. The resultant mixture is allowed to stir at −78° C. for 30 minutes, then at −20° C. for another 30 minutes. Aqueous Na2CO3 solution (2 M, 6.09 mL) is added to the mixture, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocene (169 mg, 0.304 mmol), palladium(II) acetate (68.3 mg, 0.304 mmol) and 2,4,5-trichloropyrimidine (1.12 g, 6.09 mmol). Then the reaction mixture is heated to reflux for 18 hours. At ambient temperature CH3OH (10 mL) and CHCl3 (90 mL) are added to the mixture. The organic layer is separated, dried over MgSO4, filtered, and concentrated. After chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%, the title compound is obtained as a yellowish solid (40 mg) and 872 mg starting 7-methoxy-benzo[b]thiophene is recovered.

1. waitat −20° C. for another 30 minutes
2. temperatureThen the reaction mixture is heated
3. temperatureto reflux for 18 hours
4. customThe organic layer is separated
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customAfter chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%

ORD-Eintrag

ord-502d63a8c9184c2ba7e45983fdf60305

Quelldatensatz

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07547691B2