Diisopropylethylamine → N1-(3-Fluoro-4-(2-(2-morpholinoethylamino)pyridin-4-yloxy)phenyl)-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	N1-(4-(2-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide	HCID 59852883	—
Reactant	4-(4-Amino-2-fluorophenoxy)-N-(2-morpholinoethyl)pyridin-2-amine, hydrochloride salt	HCID 60209261	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N1-(3-Fluoro-4-(2-(2-morpholinoethylamino)pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide	HCID 59852917	40%

Reaction Steps

The title compound was prepared from a mixture of 4-(4-amino-2-fluorophenoxy)-N-(2-morpholinoethyl)pyridin-2-amine, hydrochloride salt (15 mg, 0.043 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (Compound B of Example 1, 10 mg, 0.052 mmol), TBTU (17 mg, 0.052 mmol), DIPEA (30 μL), and DMF (1 mL) using a similar procedure described for the preparation of Compound C of Example 1. The crude product was purified by preparative HPLC (Shimadzu S5 VP-ODS 20×100 mm). The product obtained from HPLC purification was treated with 1 M HCl and lyophilized to give the title compound (10 mg, 40%) as a white solid. 1H NMR (DMSO-d6) δ 10.37 (s, 1H), 10.05 (s, 1H), 9.90 (br s, 1H), 7.90 (d, 1H, J=6.1 Hz), 7.75 (d, 1H, J=13.2 Hz), 7.58-7.55 (m, 2H), 7.53-7.50 (m, 1H), 7.40 (d, 1H, J=8.8 Hz), 7.24 (t, 1H, J=8.8 Hz), 7.08-7.03 (m, 3H), 6.39 (d, 1H, J=6.1 Hz), 6.11 (s, 1H), 3.80-3.81 (m, 4H), 3.67-3.65 (m, 2H), 3.47 (br s, 2H), 3.20 (br s, 4H); MS(ESI+) m/z 512.12 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07714138B2
Source dataset	uspto-grants-2010_05
ORD ID	ord-5b2cee5838f64677a0e65808de1a82ca
Source note	uspto-grants-2010_05