Hydrochloric Acid → 3-{8-[4-(Morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzoic acid

温度

95 °C

The bromide (8) (2,46 mmol) is dissolved in 10 mL DME (ethylene glycol, dimethyl ether) in a sealable pressure vessel and N2 is bubbled through for 10 min. Tetrakis(triphenylphosphine)palladium (0.24 mmol) is added and N2 is bubbled through the reaction for another 10 minutes. 3-Carboxyphenyl boronic acid (3.1 mmol) and 1N Na2CO3 solution (10 mL) are then added, the vessel sealed, and the reaction heated to 95° C. for 16 hrs. with vigorous stirring. After cooling to room temperature, the reaction is acidified to pH 3 with 1N HCl and extracted with ethyl acetate (3×25 mL). The pooled ethyl acetate layers are washed with brine, dried over sodium sulfate, and the solvent removed in vacuo. The resulting solid is then dissolved in a minimal volume of CH2Cl2 and precipitated out as a whitish-tan solid by slow addition of ethyl acetate (5 mL) followed by hexanes (30 mL) to yield 3-{8-[4-(Morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzoic acid (9).

1. customN2 is bubbled through for 10 min
2. customN2 is bubbled through the reaction for another 10 minutes
3. customthe vessel sealed
4. temperatureAfter cooling to room temperature
5. extractionextracted with ethyl acetate (3×25 mL)
6. washThe pooled ethyl acetate layers are washed with brine
7. dry with materialdried over sodium sulfate
8. customthe solvent removed in vacuo
9. dissolutionThe resulting solid is then dissolved in a minimal volume of CH2Cl2
10. customprecipitated out as a whitish-tan solid by slow addition of ethyl acetate (5 mL)

ORDレコード

ord-c498ec2c4a4b4c5d8b7ca5d8da766917

出典データセット

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07405295B2