2,6-Difluorobenzaldehyde → 1-Isopropylsulfonyl-2-amino-6-(2-(2,6-difluorophenyl)-5-(phenyl)-oxazol-4-yl)-benzimidazole

温度

100 °C

To a solution of 1-isopropylsulfonyl-2-amino-6-(α-((tert-butyldimethylsilyl)oxy)-α-(phenyl)acetyl)-benzimidazole (5.84 g, 12.0 mmol) in acetic acid (glacial, 100 mL) add ammonium acetate (9.26 g, 120 mmol) and copper (I) acetate (4.31 g, 23.7 mmol), followed by 2,6-difluorobenzaldehyde (1.41 mL, 13.1 mmol), and stir the mixture at 100° C. for 4 hours. Cool the mixture to 0° C. and slowly pour over a mixture of NH4Cl/NH4OH 3:1, pH=9. Dilute the mixture with H2O (200 mL), extract with EtOAc (3×200 mL), wash with saturated aqueous NaCl (150 mL), dry (Na2SO4), and concentrate in vacuo. Purify the residue in a biotage system (eluent:CH2Cl2/MeCN 5:1), and then by HPLC, to afford a yellow solid, 675 mg, 11% yield. MS(ES+): m/z=495.0 (M+H)+

1. temperatureCool the mixture to 0° C.
2. extractionextract with EtOAc (3×200 mL)
3. washwash with saturated aqueous NaCl (150 mL)
4. dry with materialdry (Na2SO4)
5. concentrationconcentrate in vacuo
6. customPurify the residue in a biotage system (eluent:CH2Cl2/MeCN 5:1)
7. customby HPLC, to afford a yellow solid, 675 mg, 11% yield

ORDレコード

ord-9a939b2cb85a487c8f4a15b9825ce65d

出典データセット

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07320995B2