Potassium Phosphate, Tribasic → (R)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazine-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	Sodium Acetate	HCID 517045	—
Reactant	2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde	HCID 86683915	—
Reactant	1-methyl-3-[[5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one	HCID 86683919	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Acetonitrile	HCID 6342	—
Product	(R)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazine-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde	HCID 86683920	34%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A mixture of 106a (260.0 mg, 0.56 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (200.0 mg, 0.56 mmol), PdCl2(dppf) (50.0 mg, 0.056 mmol), NaOAc (90.0 mg, 1.1 mmol), K3PO4 (300 mg, 1.1 mmol) in acetonitrile (30 mL) was heated at 100° C. for 3 h. The solvent was evaporated in vacuo. The residue was purified by flash column chromatography eluting with CH2Cl2/methanol (10:1) to afford 106b (120 mg, 34%) as a brown solid. LCMS: [M+H]+ 679.3

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08754077B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-c8620461df4243bdba6510d8ee69b773
Source note	uspto-grants-2014_06