Diisopropylethylamine → N1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate	HCID 2733207	—
Reactant	1-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea	HCID 11538912	—
Reactant	1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea	HCID 11569893	—
Reactant	N-(4-Fluorophenyl)-N-(4-(pyridin-4-yloxy)phenyl)malonamide	HCID 11610278	—
Reactant	N-(4-Methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine	HCID 59301603	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N1-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide	HCID 59301604	82%

Reaction Steps

The title compound was prepared from N-(4-methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine. (Compound C of Example 11, 200 mg, 0.59 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (Compound B of Example 1, 128 mg, 0.65 mmol), TBTU (228 mg, 0.71 mmol), and DIPEA (123 μL, 0.71 mmol) in DMF using a similar procedure described for the preparation of Compound C of Example 1. The crude product was purified by trituration with isopropyl ether to give the title compound (250 mg, 82%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.43 (s, 1H), 10.25 (s, 1H), 8.09 (s, 1H), 7.85 (s, 1H), 7.72 (dd, 1H, J=9.1, 5.0 Hz), 7.62 (dd, 2H, J=8.8, 5.0 Hz), 7.31-7.21 (m, 4H), 7.15 (dd, 2H, J=8.8, 8.8 Hz), 6.88 (m, 2H), 5.90 (s, 1H), 4.42 (br s, 2H), 3.71 (s, 3H), 3.46 (s, 2H); MS(ESI+) m/z 520.14 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07459562B2
Source dataset	uspto-grants-2008_12
ORD ID	ord-48747d8a37b344a8877c83d00ca3eec4
Source note	uspto-grants-2008_12