Hydrazine → HCID 118207724, compound

Participants

Reaction Conditions

Reaction Steps

To a 25 mL pear flask were added 2-amino-4-(((S)-1-(6-((R)-3-(1,3-dioxoisoindolin-2-yl)piperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile (20 mg, 0.037 mmol) and hydrazine monohydrate (0.027 mL, 0.56 mmol) in ethanol (1 mL). The mixture was heated to 60° C. for 8 hours and then at room temperature overnight. Additional hydrazine (30 eq, 0.054 mL) was added and the mixture was heated for another 4 hours. The crude reaction mixture was diluted with acetonitrile and was then purified by preparative HPLC (basic mode, 20-45% ACN/water gradient). The product-containing fractions were combined and lyophilized to give the title compound as a light brown solid (4.0 mg, 28%). The absolute configuration of the stereocenter on the piperidine ring was not determined, but was assigned the opposite configuration of EXAMPLE 5. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (d, J=6.57 Hz, 3H), 1.72-1.99 (m, 3H), 2.09-2.22 (m, 1H), 2.27-2.36 (m, 3H), 2.56-2.73 (m, 3H), 3.47 (ddd, J=9.09, 7.20, 4.93 Hz, 1H), 3.59-3.66 (m, 1H), 3.67-3.73 (m, 3H), 5.19 (br s, 2H), 5.77-5.95 (m, 1H), 6.57 (d, J=3.28 Hz, 1H), 6.93-7.07 (m, 1H), 7.12-7.16 (m, 1H), 7.17-7.23 (m, 2H), 7.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C21H27N9, 406. found 406.

Provenance & Evidence