(1S)-(+)-Camphor-10-sulphonic acid → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-[6-(2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyrimidin-4-yl]-1-methylurea

After adding (1S)-(+)-10-camphorsulfonic acid (101 mg) to a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (110 mg) in ethanol (2.0 ml), the mixture was stirred for 15 minutes at room temperature. After adding 2-(4-fluorophenyl)acetyl isothiocyanate (3.06 ml, 0.25 M solution in toluene) thereto, the mixture was further stirred at room temperature for 1 hour. The reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml). The organic layer was washed with brine and dried over anhydrous sodium sulfate. The dried organic layer was concentrated and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated. Diethyl ether:hexane=1:1 was added to the obtained solid to produce a suspension. The precipitate was filtered and then washed with diethyl ether to provide the title compound (50.5 mg, 31.6%) as pale yellow powder.

1. stirringthe mixture was further stirred at room temperature for 1 hour
2. customThe reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml)
3. washThe organic layer was washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationThe dried organic layer was concentrated
6. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
7. additionFractions containing the target compound
8. concentrationwere concentrated
9. additionDiethyl ether:hexane=1:1 was added to the obtained solid
10. customto produce a suspension
11. filtrationThe precipitate was filtered
12. washwashed with diethyl ether

ORDレコード

ord-9210bba8a09a41c7948a916c89bebbbe

出典データセット

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07531532B2