Methanol → 4-[5-(Bromomethyl)-1,3-oxazol-2-yl]-6-chloro-1-(phenylsulfonyl)-1H-indazole

Temperatur

3 °C

(2-(6-Chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazol-5-yl)methanol (1.0 eq., 1 wt, 34.0 g) and triphenylphosphine dibromide (1.3 eq., 1.32 wt, 45.0 g) are stirred in dichloromethane (15 vols, 510 ml) at 20 (±3° C.) under a nitrogen atmosphere for 1 hr. The reaction is then checked by HPLC for completion. Once complete methanol (0.8 vols, 27.2 ml) is added to the reaction, with vigorous stirring 8% w/w sodium hydrogen carbonate solution (10 vols, 340 ml) is added drop wise over 15 minutes (check aqueous pH>7). The mixture is heated to 3° C. (±3° C.) and stirred together for 10 minutes, then separated, the aqueous is back extracted with dichloromethane (5 vols, 170 ml) and the combined dichloromethane layers are washed with water (5 vols, 170 ml). The dichloromethane solution is then evaporated under reduced pressure to a volume of approximately 4 vols. To the solution is added methanol (15 vols, 510 ml) and the solution evaporated under reduced pressure at 260 mbar, 20° C. to remove the remaining dichloromethane down to ˜15 vols. The suspension is then stirred at 20° C. for at least 6 hrs. The solid is filtered, washed with methanol (2×1 vols, 2×34 ml), sucked dry for 20 minutes, then dried under high vacuum at 30° C. (±3° C.) to constant probe temperature to afford 5-(bromomethyl)-2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazole as a beige solid.

1. additionis added drop wise over 15 minutes (check aqueous pH>7)
2. customseparated
3. extractionthe aqueous is back extracted with dichloromethane (5 vols, 170 ml)
4. washthe combined dichloromethane layers are washed with water (5 vols, 170 ml)
5. customThe dichloromethane solution is then evaporated under reduced pressure to a volume of approximately 4 vols
6. additionTo the solution is added methanol (15 vols, 510 ml)
7. customthe solution evaporated under reduced pressure at 260 mbar, 20° C.
8. customto remove the remaining dichloromethane down to ˜15 vols
9. stirringThe suspension is then stirred at 20° C. for at least 6 hrs
10. filtrationThe solid is filtered
11. washwashed with methanol (2×1 vols, 2×34 ml)
12. customsucked dry for 20 minutes
13. customdried under high vacuum at 30° C. (±3° C.) to constant probe temperature

ORD-Eintrag

ord-ffe4c85a442e462798e444fa8530839d

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09102668B2