Methoxytrimethylsilane → 6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

Participants

Role	Name	HCID	Charge
Reactant	Methoxytrimethylsilane	HCID 15771	—
Reactant	(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected	HCID 1514389	—
Reactant	6-Chloro-4-(5,6-dimethoxypyridin-2-ylamino)pyridazine-3-carboxamide	HCID 86689746	—
Solvent	N-methyl-2-pyrrolidone	HCID 13387	—
Product	6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide	HCID 71626968	35.5%

Reaction Conditions

Temperature	150 °C

Reaction Steps

To 6-chloro-4-(5,6-dimethoxypyridin-2-ylamino)pyridazine-3-carboxamide (500 mg, 1.6 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (692 mg, 3.2 mmol) in NMP (1.5 mL), methoxy trimethylsilane (0.5 mL, 3.6 mmol) was added and the mixture heated to 150° C. for 65 h. The mixture was concentrated under high vacuum to obtain a sticky crude mass that was purified by chromatography (silica, 100-200 mesh, 1-10% methanol in dichloromethane) to give 6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (220 mg 35%) as a yellow solid. LC-MS 388 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08901124B2
Source dataset	uspto-grants-2014_12
ORD ID	ord-17738304fb05476ab3adc0b706c23573
Source note	uspto-grants-2014_12