Potassium Phosphate, Tribasic → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]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 Trihydrate	HCID 23665404	—
Reactant	2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde	HCID 86683915	—
Reactant	1-Methyl-3-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one	HCID 86683938	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Acetonitrile--water (1/1)	HCID 18373917	—
Product	2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde	HCID 86683937	42%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A round-bottomed flask equipped with a reflux condenser was charged with 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (144 mg, 0.40 mmol), 115c (240 mg, 0.60 mmol), PdCl2(dppf) (20 mg, 0.020 mmol), K3PO4 (180 mg, 0.80 mmol), sodium acetate trihydrate (120 mg, 0.80 mmol), and acetonitrile/water (15 mL/1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 25:1 dichloromethane/methanol to afford 115d as a yellow solid (100 mg, 42%). MS-ESI: [M+H]+ 600.3

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08754077B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-737c28c61dca4bd0bdaac65edf52c77f
Source note	uspto-grants-2014_06