4-Fluorobenzoic Acid → HCID 178489757, Verbindung

Temperatur

0 °C

Oxalyl chloride (2M in DCM, 1.40 ml, 2.75 mmol, 1.1 eq) was added dropwise to a mixture of 4-fluorobenzoic acid (350 mg, 2.50 mmol, 1 eq) in dichloromethane (15 ml) at 0° C. containing a few drops of DMF (10 ul, 0.12 mmol, 0.05 eq) and DIPEA (937 μl, 5.25 mmol, 2.1 eq). After stirring for 60 mins at 0° C. a solution of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (742 mg, 3 mmol, 1.2 eq) in DCM (10 ml) was added dropwise over 15 mins. The mixture was maintained at 0° C. for a further 2 h, then gradually allowed to warm to room temperature overnight. The mixture was diluted with DCM (50 ml) and washed with aqueous NaHCO3 solution (50 ml). The aqueous layer was extracted with DCM (50 ml). The combined organic layers were collected and concentrated. The crude product was purified by reverse-phase prep HPLC using a 30-50% gradient of acetonitrile in water containing 1% ammonium hydroxide solution. The desired fractions were evaporated to afford the title compound as a beige solid. (31.5 mg, 3% yield)

1. additionwas added dropwise over 15 mins
2. temperatureto warm to room temperature overnight
3. washwashed with aqueous NaHCO3 solution (50 ml)
4. extractionThe aqueous layer was extracted with DCM (50 ml)
5. customThe combined organic layers were collected
6. concentrationconcentrated
7. customThe crude product was purified by reverse-phase prep HPLC
8. customThe desired fractions were evaporated

ORD-Eintrag

ord-1e71506f710044cbbbadcf5045c78d46

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07737149B2