تفاعل #73883

معادلة التفاعل

1-(4′-{3-methyl-4-[5-(3-methyl-phenyl)-pyridin-3-ylamino]-isoxazol-5-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid

DMF

oxalyl chloride

methanesulfonamide

DIEA

→

title compound

N-(1-{4′-[3-Methyl-4-(5-(3-methyl-phenyl)-pyridin-3-ylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarbonyl)-methanesulfonamide

المذيبات

EtOAc

DCM

ظروف التفاعل

المعالجة

1. 1
   تركيزthe mixture was concentrated to dryness
2. 2
   workup.DISSOLUTIONre-dissolved in DCM (1 mL)
3. 3
   استخلاصextracted with H2O (2×10 mL)
4. 4
   استخلاصThe combined aqueous layers were back-extracted with EtOAc (10 mL)
5. 5
   تجفيفThe combined organic layers were dried over MgSO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe crude residue was purified on reverse-phase preparative HPLC

الإجراء التجريبي

To a stirred solution of 1-(4′-{3-methyl-4-[5-(3-methyl-phenyl)-pyridin-3-ylamino]-isoxazol-5-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid (0.050 g, 0.1 mmol) in DCM (1 mL) at RT was added DMF (1 μL, 0.01 mmol) and oxalyl chloride (17 μL, 0.15 mmol). After 1 hr, the mixture was concentrated to dryness and re-dissolved in DCM (1 mL). To this solution was added methanesulfonamide (0.014 g, 0.15 mmol), DIEA (60 μL, 0.35 mmol), and DMAP (0.001 g). The resulting mixture was stirred for 5 min, then diluted with EtOAc (20 mL) and extracted with H2O (2×10 mL). The combined aqueous layers were back-extracted with EtOAc (10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude residue was purified on reverse-phase preparative HPLC to afford the title compound.

المصدر