Sodium triacetoxyborohydride → HCID 178448323, compound

3-amino-5-phenyl pyrazole (31.2 mmol) was combined with (S)-2-tert-butoxycarbonylamino-pentanoic acid (37.5 mmol) and dissolved in 50 mL of anhydrous dichloromethane. Triethylamine (93.6 mmol) was added, followed by TBTU (37.5 mmol) and the reaction mixture was stirred at rt for 2 h. The solution was then diluted with 50 mL of fresh dichloromethane and extracted with 50 mL portions of aqueous saturated bicarbonate solution, water and then brine. The organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified through flash chromatography on silica gel. The purified product was then heated neat at 150° C. for 3 h. The reaction mixture (14.4 mmol) was then cooled to rt and dissolved in 40 mL of anhydrous 4.0 N HCl dioxane solution and stirred at rt for 3 h. The reactions were concentrated under reduced pressure and triturated with 20 mL of anhydrous Et2O. The solids were filtered and dried to give the desired amine, (S)-2-Amino-pentanoic acid (5-phenyl-2H-pyrazol-3-yl)-amide. 2-(2,3-Difluoro-phenyl)-acetaldehyde (0.2 mmol) was combined with (S)-2-Amino-pentanoic acid (5-phenyl-2H-pyrazol-3-yl)-amide (0.2 mmol) in 2 mL of anhydrous dichloromethane under N2. Sodium triacetoxyborohydride (0.3 mmol) and two drops of acetic acid were then added and the reaction was stirred at rt for 16 h. The crude solution was then concentrated under reduced pressure and purified through flash chromatography on silica gel to give 2-(S)-[2-(2,3-Difluoro-phenyl)ethylamino]-pentanoic acid (5-phenyl-2H-pyrazol-3-yl)-amide, LC-MS 2.7 min, 398 [M+1].

1. concentrationThe crude solution was then concentrated under reduced pressure
2. custompurified through flash chromatography on silica gel

ORD record

ord-9d4586ef54ae4ff8a923366bb805864d

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468386B2