HCID 86760736, compound → HCID 69311989, compound

n-Butyl lithium (656 μl of a 1.6 N solution in hexane, 1.05 mmol), was added dropwise to a solution of ethyl triphenylphosphonium iodide (437 mg, 1.05 mmol), in anhydrous THF (15 ml), under nitrogen at 0° C. A solution of 4-(2-formyl-1-isopropylimidazol-5-yl)-2-{4-[N-(2-methoxyethyl)-N-(2-trimethylsilylethoxymethyl)sulphamoyl]anilino}pyrimidine (Method 105; 300 mg, 0.523 mmol), in THF (5 ml), was then slowly added. The mixture was allowed to warm to ambient temperature and stirred for 18 hours. The volatiles were removed by evaporation and the residue dissolved in EtOAc (40 ml), washed with water (2×15 ml), brine (15 ml), and dried. The solvent removed by evaporation to give a crude product (254 mg), as a yellow foam. The crude product was purified by chromatography on silica-gel eluting with 3% MeOH in DCM), the semi-pure product (70 mg), was dissolved in TFA/H2O (1:1, 10 ml), and stirred for 1 hour. The TFA was removed by evaporation, the resulting aqueous solution neutralised with saturated NaHCO3, and the product extracted with DCM (3×5 ml). The extracts were combined, dried and the solvent removed. The residue was purified by preparative reverse phase HPLC, eluting with acetonitrile/H2O, 0.01% formic buffer. Pure fractions were neutralised with 2N aqueous sodium hydroxide solution. The resulting white precipitate, was collected by filtration and dried to give the title compound (1:2.5 mixture of E:Z isomers), as a white solid (5 mg, 2%). NMR: Z isomer 1.51 (d, 6H), 2.09 (d, 3H), 2.92 (t, 2H), 3.17 (s, 3H), 3.33 (t, 2H), 5.60 (m, 1H), 6.05 (m, 1H), 6.51 (m, 1H), 7.1 (br s, 1H), 7.16 (d, 1H), 7.57 (s, 1H), 7.71 (d, 2H), 7.88 (d, 2H), 8.48 (d, 1H), 9.47 (s, 1H); E isomer 1.51 (d, 6H), 1.94 (d, 3H), 2.92 (t, 2H), 3.17 (s, 3H), 3.33 (t, 2H), 5.60 (m, 1H), 6.60 (m, 1H), 6.67 (m, 1H), 7.1 (br s, 1H), 7.13 (d, 1H), 7.47 (s, 1H), 7.71 (d, 2H), 7.88 (d, 2H), 8.44 (d, 1H), 9.47 (s, 1H); m/z: 457.

1. customThe volatiles were removed by evaporation
2. dissolutionthe residue dissolved in EtOAc (40 ml)
3. washwashed with water (2×15 ml), brine (15 ml)
4. customdried
5. customThe solvent removed by evaporation
6. customto give a crude product (254 mg)
7. customThe crude product was purified by chromatography on silica-gel
8. washeluting with 3% MeOH in DCM), the semi-pure product (70 mg)
9. dissolutionwas dissolved in TFA/H2O (1:1, 10 ml)
10. stirringstirred for 1 hour
11. customThe TFA was removed by evaporation
12. extractionthe product extracted with DCM (3×5 ml)
13. customdried
14. customthe solvent removed
15. customThe residue was purified by preparative reverse phase HPLC
16. washeluting with acetonitrile/H2O, 0.01% formic buffer
17. filtrationThe resulting white precipitate, was collected by filtration
18. customdried

ORD record

ord-5dd1030080f04f4e88864765bf08cd16

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07442697B2