Toluene → 2-(3-Chloro-4-fluorophenyl)-N5-(3,3-dimethylcyclobutyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide

Temperatur

90 °C

To a stirred solution of Intermediate 285D (13 mg, 0.1 mmol) in toluene (2 ml) was added TEA (0.071 ml, 0.509 mmol), DPPA (0.028 ml, 0.122 mmol) and the reaction mixture was heated to 90° C. for 1 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in DMF (1 mL) and stirred at RT for 16 h. The reaction mixture was quenched with 10% NaHCO3 and extracted with ethyl acetate (2×20 mL). The combined organic layer was dried over Na2SO4, filtered and the filtrate evaporated under reduced pressure. The crude product was purified by preparative HPLC to afford Compound 285 (20 mg, 46%). HPLC retention times 9.40 min. and 8.50 min (Methods A and B respectively). MS(ES): m/z=420 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.81-7.90 (m, 1H), 7.64-7.74 (m, 1H), 7.42-7.46 (m, 1H), 7.14-7.40 (d, 2H), 6.98 (s, 1H), 4.72 (s, 2H), 4.06-4.20 (m, 3H), 3.82 (t, J=5.27 Hz, 2H), 1.95-2.05 (m, 2H), 1.72-1.83 (m, 2H), 1.11 (d, J=7.53 Hz, 6H).

1. temperatureThe reaction mixture was cooled to RT and to it
2. customThe reaction mixture was quenched with 10% NaHCO3
3. extractionextracted with ethyl acetate (2×20 mL)
4. dry with materialThe combined organic layer was dried over Na2SO4
5. filtrationfiltered
6. customthe filtrate evaporated under reduced pressure
7. customThe crude product was purified by preparative HPLC

ORD-Eintrag

ord-20b3f2a2b39b406793ae5de6d2dfd515

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273058B2