Diisopropylethylamine → 5-(5-Chlorothiophen-2-yl)-4-(2-fluorobenzyl)-2-({3-[2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Under argon, 95 mg (0.18 mmol) of benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate were added to a solution of 56 mg (0.15 mmol) of [3-(5-chloro-2-thienyl)-4-(2-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetic acid [preparation according to WO 2007/134862 Example 154A] and 32 μl (0.18 mmol) of N,N-diisopropylethylamine in 1.5 ml of dry DMF. After 20 min of stirring, 34 mg (0.17 mmol) of N′-hydroxy-2-(trifluoromethyl)benzene-carboximidamide were added. The mixture was then stirred at RT for 16 h. For work-up, 10 ml of water were added and the mixture was extracted three times with in each case 10 ml of ethyl acetate. The combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution, filtered through Extrelut and concentrated under reduced pressure. The residue was dissolved in 2 ml of DMF and stirred in a microwave oven at 250° C. for 15 min. After cooling, the solvent was removed under reduced pressure on a rotary evaporator and the crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1). This gave 60 mg (72% of theory) of the target compound as a yellow resin.

1. stirringThe mixture was then stirred at RT for 16 h
2. extractionthe mixture was extracted three times with in each case 10 ml of ethyl acetate
3. washThe combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution
4. filtrationfiltered through Extrelut
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved in 2 ml of DMF
7. stirringstirred in a microwave oven at 250° C. for 15 min
8. temperatureAfter cooling
9. customthe solvent was removed under reduced pressure on a rotary evaporator
10. customthe crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1)

ORDレコード

ord-91142aa966594d3fa21f238a0415a990

出典データセット

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09187466B2