3-(tert-butylamino)propanoic acid;hydrochloride

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

実験手順: To a stirred solution of 11-7 (275 mg, 0.79 mmoles), HOBT (130 mg, 0.95 mmoles), N(i-Pr)2Et (0.55 mL, 3.2 mmoles), tert-butyl-β-alanine hydrochloride (160 mg, 0.95 mmoles), and DMF (4 mL), at -15° C. was added EDC (183 mg, 0.95 mmoles) followed by removal of the cooling bath. After 20 hours the reaction mixture was diluted with EtOAc and then washed with H2O, saturated NaHCO3, 10% KHSO4, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 50% EtOAc/hexanes) gave 11-8 as a colorless oil. Rf 0.21 (silica, 50% EtOAc/hexanes). followed by removal of the cooling bath After 20 hours the reaction mixture was diluted with EtOAc washed with H2O, saturated NaHCO3, 10% KHSO4, and brine dried (MgSO4) concentrated

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

実験手順: To a stirred solution of 11-7 (275 mg, 0.79 mmoles), HOBT (130 mg, 0.95 mmoles), N(i-Pr)2Et (0.55 mL, 3.2 mmoles), tert-butyl-β-alanine hydrochloride (160 mg, 0.95 mmoles), and DMF (4 mL), at -15° C. was added EDC (183 mg, 0.95 mmoles) followed by removal of the cooling bath. After 20 hours the reaction mixture was diluted with EtOAc and then washed with H2O, saturated NaHCO3, 10% KHSO4, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 50% EtOAc/hexanes) gave 11-8 as a colorless oil. Rf 0.21 (silica, 50% EtOAc/hexanes). followed by removal of the cooling bath After 20 hours the reaction mixture was diluted with EtOAc washed with H2O, saturated NaHCO3, 10% KHSO4, and brine dried (MgSO4) concentrated

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

実験手順: To a stirred solution of 11-7 (275 mg, 0.79 mmoles), HOBT (130 mg, 0.95 mmoles), N(i-Pr)2Et (0.55 mL, 3.2 mmoles), tert-butyl-β-alanine hydrochloride (160 mg, 0.95 mmoles), and DMF (4 mL), at -15° C. was added EDC (183 mg, 0.95 mmoles) followed by removal of the cooling bath. After 20 hours the reaction mixture was diluted with EtOAc and then washed with H2O, saturated NaHCO3, 10% KHSO4, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 50% EtOAc/hexanes) gave 11-8 as a colorless oil. Rf 0.21 (silica, 50% EtOAc/hexanes). followed by removal of the cooling bath After 20 hours the reaction mixture was diluted with EtOAc washed with H2O, saturated NaHCO3, 10% KHSO4, and brine dried (MgSO4) concentrated

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

実験手順: A solution of PyBOP (38 mg, 70 umol) in DMF (0.1 ml) was added to a mixture of 4-({3-(3,5-dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoic acid (20 mg, 36 umol), tert-butyl β-alanine hydrochloride (27 mg, 4 eq.), DIEA (40 ul, 6 eq.) in DMF (0.3 ml). The reaction was quenched with CH3CN:water (5% TFA) and purified with reverse phase HPLC to give tert-butyl N-[4-({3-(3,5-dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoyl]-β-alaninate as an oil residue. This was treated with TFA/DCM (1:2) and the product was lyophilized to give N-[4-({3-(3,5-Dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoyl]-β-alanine as a white powder. NMR (500 MHz, DMSO-d6) δ: 2.43 (t, 2H); 3.4 (q, 2H); 6.18 (s, 2H); 7.26 (br d, J=9.2 Hz, 1H); 7.38 (d, J=8.5 Hz, 2H); 7.59 (s, 1H); 7.61 (t, J=1.9 Hz, 1H); 7.67 (br s, 1H); 7.72 (d, J=8.5 Hz, 2H); 7.74 (br d, J=9.2 Hz, 1H); 7.82 (d, J=1.9 Hz, 2H). MS Cald for C28H20Cl2F3N5O4: 617.08; Obsd (M+1): 618.21. The reaction was quenched with CH3CN water (5% TFA) and purified with reverse phase HPLC

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

実験手順: To a stirred solution of 11-7 (275 mg, 0.79 mmoles), HOBT (130 mg, 0.95 mmoles), N(i-Pr)2Et (0.55 mL, 3.2 mmoles), tert-butyl-β-alanine hydrochloride (160 mg, 0.95 mmoles), and DMF (4 mL), at -15° C. was added EDC (183 mg, 0.95 mmoles) followed by removal of the cooling bath. After 20 hours the reaction mixture was diluted with EtOAc and then washed with H2O, saturated NaHCO3, 10% KHSO4, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 50% EtOAc/hexanes) gave 11-8 as a colorless oil. Rf 0.21 (silica, 50% EtOAc/hexanes). followed by removal of the cooling bath After 20 hours the reaction mixture was diluted with EtOAc washed with H2O, saturated NaHCO3, 10% KHSO4, and brine dried (MgSO4) concentrated