3-(2,5-Dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine → 2-[4-[4-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]ethanol

Temperature

140 °C

3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (200 mg, 0.75 mmol), 2-(4-(4-amino-3-methoxyphenyl)piperazin-1-yl)ethanol (190 mg, 0.75 mmol), cesium carbonate (295 mg, 0.91 mmol), diacetoxypalladium (13.55 mg, 0.06 mmol) and (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T- BUTYLPHOSPHINE (41.8 mg, 0.08 mmol) were suspended in DME (5 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 140 °C over a period of 30 minutes in the microwave reactor. The reaction mixture was filtratet and the fitrate was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(4-(4-(5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazin-1-yl)ethanol (60mg) 1H NMR 01570-55-03 as a red gum. The gum was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 2-(4-(4-(5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazin-1-yl)ethanol (40.0 mg, 11.05 %) as a yellow foam.

ORD record

ord-b16c1805f7d5406ba2f0d69bfae1736b

Source dataset

750 AstraZeneca ELN dataset

Original link

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