Dimethylacetamide → Tert-butyl (6-(2-(dimethylamino)thiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

Participants

Role	Name	HCID	Charge
Reactant	Dimethylacetamide	HCID 31374	—
Reactant	5-bromo-N,N-dimethyl-1,3-thiazol-2-amine	HCID 12448555	—
Reactant	tert-Butyl ((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate	HCID 57691389	—
Reactant	HCID 178461732	HCID 178461732	—
Catalyst	Zincchloride	HCID 3007855	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Catalyst	Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene	HCID 129828017	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	Tert-butyl (6-(2-(dimethylamino)thiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate	HCID 57691069	71.9%

Reaction Steps

To a solution of 5-bromo-N,N-dimethylthiazol-2-amine (0.73 g, 3.53 mmol) in anhydrous THF (9 mL) was added isopropylmagnesium lithium chloride (1.0 M in THF, 4.8 mL, 4.8 mmol) at −40° C. The solution was stirred for twenty minutes followed by the dropwise addition of zinc chloride (0.5 M in THF, 10 mL, 5.2 mmol). The mixture was brought to room temperature and stirred for thirty minutes followed by the addition of dimethylacetamide (12 mL), Pd2(dba)3, (0.32 g, 0.35 mmol), Q-Phos (0.34 g, 0.56 mmol), and tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (0.29 g, 1.0 mmol). The mixture was stirred at 50° for two hours then was quenched with saturated ammonium chloride and purified by MPLC chromatography (eluted with a gradient of 0 to 10% (1:10:90 NHIOH:MeOH:DCM) in DCM) to yield the product as a light orange solid (0.27 g, 71%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09066954B2
Source dataset	uspto-grants-2015_06
ORD ID	ord-51a6bbd95b3d4bb3a577bae01cd1c9b1
Source note	uspto-grants-2015_06