(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution of 6-chloro-4-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazine-3-carboxamide (375 mg, 1.29 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (555 mg, 2.59 mmol) in N-methyl-2-pyrrolidinone (3 mL) was treated with tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (555 mg, 2.59 mmol), The reaction mixture was heated at 120° C. for 72 h, then cooled to room temperature, concentrated under high vacuum and the residue obtained was purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 5% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 20 min) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (444 mg, 73%) as a light brown foam. 1H NMR (CHLOROFORM-d) δ: 11.30 (s, 1H), 8.19 (s, 1H), 8.06 (d, J=3.4 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 6.75-7.10 (m, 1H), 6.61 (d, J=8.3 Hz, 1H), 5.77-6.14 (m, 2H), 3.99 (m, 1H), 3.55-3.74 (m, 1H), 2.67-3.05 (m, 4H), 2.11 (quin, J=7.5 Hz, 2H), 1.18-2.01 (m, 17H); LC-MS 468.2 [M+H]+.

Provenance & Evidence