Diisopropylamine → (3-{4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylamine	HCID 7912	—
Reactant	tert-butyl N-(prop-2-yn-1-yl)carbamate	HCID 11073648	—
Reactant	[1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride	HCID 66623800	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	HCID 178418397	HCID 178418397	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	(3-{4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester	HCID 66623769	89.3%

Reaction Steps

[1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.334 g, 0.628 mmol) and Prop-2-ynyl-carbamic acid tert-butyl ester (113 mg, 1.16 equiv.) is treated with i-Pr2NH (2 equiv.) in dry THF (4 ml) under N2. Pd(PPh3)4 (25 mg, 0.0356 mmol, 5.7 mol %) and solid CuI (5 mol %) are added next, and the mixture is stirred at r.t. for 3 hours. Workup: THF is removed under reduced pressure and DCM (10 ml) is added. The organic layer is washed with sat. aq. NH4Cl solution and brine, dried and concentrated. Chromatography on silica (EtOAc/hexanes) affords the desired pure product (293 mg, 89%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08088766B2
Source dataset	uspto-grants-2012_01
ORD ID	ord-5957178150f44cb5b1bad6373a09372f
Source note	uspto-grants-2012_01