Lithium Hydroxide → N-[2-[[6-[[5-[2-(6-tert-butyl-8-fluoro-1-oxo-phthalazin-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]prop-2-enamide

Participants

Role	Name	HCID	Charge
Reactant	Lithium Hydroxide	HCID 3939	—
Reactant	(4-(5-(6-(2-acrylamidoethoxyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate	HCID 118116891	—
Solvent	Tetrahydrofuran water isopropanol	HCID 22722550	—
Product	N-[2-[[6-[[5-[2-(6-tert-butyl-8-fluoro-1-oxo-phthalazin-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]prop-2-enamide	HCID 118116889	10%

Reaction Steps

A mixture of 104d (140 mg, 0.21 mmol) and LiOH (44 mg, 1.05 mmol) in THF/i-PrOH/water (2.0 mL/1.2 mL/0.8 mL) was stirred at rt for 1 h. The mixture was extracted with EA. The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by prep-HPLC to give 104 (10 mg, 10% for two steps) as a light yellow solid. 1H NMR (500 MHz, CDCl3): δ 8.72-8.66 (m, 2H), 8.33 (s, 1H), 7.91 (s, 1H), 7.59-7.47 (m, 6H), 6.51 (s, 1H), 6.44 (d, J=10.0 Hz, 1H), 6.24-6.16 (m, 2H), 5.99-5.94 (m, 1H), 5.50 (d, J=10.0 Hz, 1H), 4.58-4.48 (m, 2H), 4.28-4.21 (m, 2H), 3.99-3.57 (m, 5H), 1.43 (s, 9H). MS-ESI: [M+H]+ 640.3

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09260415B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-85bdc4895cda4825a7843b5b517512ca
Source note	uspto-grants-2016_02