1,1,3-tributylthiourea

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 2a from 4-bromo-2-methylbenzoic acid, pyrrolidine, tBtU and N-ethyl-diisopropylamine in tetrahydrofuran/water 9:1

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 2-bromopropionate (0.0001 mol) was added to a mixture of intermediate (12) (0.000084 mol) and tri-n-butylthiourea (TBTU) (0.000168 mol) in DIPEA (4 ml). The reaction mixture was shaken for 2 hours at 70° C. The reaction mixture was cooled to room temperature, filtered and the filtrate was evaporated. The residue was dissolved in DCM (4 ml), then washed with water (2 ml). The mixture was filtered through Extrelut™ and the filter residue was washed with DCM (2×3 ml). The filtrate was evaporated. The residue was purified by HPLC (Waters column, with Xterra MS C18; eluent: [(0.5% NH4OAc in H2O)/CH3CN 90/10)]/CH3CN (0 min) 85/15, (10 min) 10/90, (16 min) 0/100, (18.10-20.00 min) 85/15), yielding 1-piperidineacetic acid, α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-, 2-ethoxy-1-methyl-2-oxoethyl ester (compound 111). The reaction mixture was cooled to room temperature filtered the filtrate was evaporated The residue was dissolved in DCM (4 ml) washed with water (2 ml) The mixture was filtered through Extrelut™ the filter residue was washed with DCM (2×3 ml) The filtrate was evaporated The residue was purified by HPLC (Waters column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 2a from 4-bromo-2-methylbenzoic acid, pyrrolidine, tBtU and N-ethyl-diisopropylamine in tetrahydrofuran/water 9:1