Sodium Carbonate → N-[6-(5-Amino-6-chloro-3-pyridinyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	1,4-Dioxane	HCID 31275	—
Reactant	3-Amino-5-bromo-2-chloropyridine	HCID 21858354	—
Reactant	2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide	HCID 58255833	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Product	N-[6-(5-Amino-6-chloro-3-pyridinyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide	HCID 58255741	45.9%

Reaction Conditions

Temperature	140 °C

Reaction Steps

2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (0.75 g), 5-bromo-2-chloro-3-pyridinamine (0.39 g), sodium carbonate (0.66 g) and Pd(dppf)Cl2 (0.114 g) were weighed to a 10-20 ml microwave vial and 1,4-dioxane (8 ml) then water (8 ml) were added. The reaction was heated at 140° C. for 20 min. The reaction was passed through a 10 g silica cartridge, washing with methanol:DCM (1:1, v/v). The solvent was evaporated and the residue was purified on a 40 g ISCO companion silica cartridge, eluting with 1.5-7.5% methanol in DCM (containing 1% ammonia) at 40 ml/min. Pure fractions were combined and evaporated to dryness to give title compound (335 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08163743B2
Source dataset	uspto-grants-2012_04
ORD ID	ord-a56ef88e29bf4aa580f67713d9f1918e
Source note	uspto-grants-2012_04