Diisopropylamine → N-[3-(6-chloro-7-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N,N',N'-trimethylurea

Participants

Reaction Steps

This was prepared using the method described in example 26 but it was carried out at room temperature over 3 hr using N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4ylpropoxy)quinazolin-4-amine (310 mg, 0.52 mmol), N,N,N′-trimethyl-N′-prop-2-yn-1-ylurea (145 mg, 1.04 mmol), bis(triphenylphosphine) palladium(II) dichloride (36 mg, 10 mol %), copper(I) iodide (10 mg, 10 mol %) and diisopropylamine (105 mg, 1.04 mmol) in ethyl acetate (10 ml). The crude product was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give the title compound (218 mg, 69%) as a pale brown solid; NMR Spectrum:(CDCl3) 2;11 (quintet, 2H), 2.48 (m, 4H), 2.56 (t, 2H), 2.87 (s, 6H), 2.92 (s, 3H), 3.72 (m, 4H), 4.00 (s, 3H), 4.15 (s, 2H), 4.25 (t, 2H), 6.06 (s, 2H), 7.03 (s, 1H), 7.10-7.30 (s(broad), 1H), 7.20 (s, 1H), 7.31 (s, 1H), 8.60 (s, 1H); Mass Spectrum: M+H+ 611/613.

Provenance & Evidence