Diisopropylethylamine → N-[(3R)-1-imidazo[1,2-a]pyrazin-8-ylpyrrolidin-3-yl]-1-phenyl-1,2,4-triazole-3-carboxamide

1-Phenyl-1,2,4-triazole-3-carboxylic acid (1.2 g, 6.3 mmol), (3R)-1-imidazo[1,2-a]pyrazin-8-ylpyrrolidin-3-amine dihydrochloride (2.0 g, 7.4 mmol), and diisopropylethylamine (13 mL, 75 mmol) were combined together in 50 mL DMF. To this mixture was added HATU (2.5 g, 6.6 mmol). After stirring 3 minutes, LCMS of an aliquot indicated the reaction was complete. DIPEA and most of the DMF were removed under reduced pressure. The residue was diluted in 400 mL EtOAc and washed with 50 mL saturated NaH2PO4. It was determined that a large amount of the desired product was present in the organic phase, therefore it was extracted with 400 mL 10 vol % i-PrOH/CHCl3. The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (SiO2, 2-5% MeOH/dichloromethane) to provide 936 mg of the desired product (39% yield). 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1 H), 7.74 (td, J=1.1, 7.5 Hz, 2 H), 7.56-7.48 (m, 4 H), 7.47-7.40 (m, 2 H), 7.37 (d, J=8.2 Hz, 1 H), 7.33 (d, J=4.3 Hz, 1 H), 5.00-4.80 (m, 1H), 4.50-4.35 (br, 1 H), 4.30-4.15 (br, 3 H), 3.45-3.30 (m, 1H), 2.90-2.75 (m, 1 H), 2.50-2.38 (m, 1 H), 2.25-2.15 (m, 1 H). MS: (ES) 375.2 (M+H+).

1. customDIPEA and most of the DMF were removed under reduced pressure
2. additionThe residue was diluted in 400 mL EtOAc
3. washwashed with 50 mL saturated NaH2PO4
4. extractionit was extracted with 400 mL 10 vol % i-PrOH/CHCl3
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by flash chromatography (SiO2, 2-5% MeOH/dichloromethane)

ORD record

ord-f95508f4145b4b12960115ced367695c

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169261B2