Diisopropylethylamine → N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-isoxazolecarboxamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,2-Oxazole-5-carboxylic acid	HCID 2060599	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile	HCID 59451392	—
Solvent	Methanol	HCID 887	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-isoxazolecarboxamide	HCID 59451543	46.2%

Reaction Steps

In a 1 dram vial, 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 5-isoxazolecarboxylic acid (9.09 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.015 g, 46%) as a white solid. 1H NMR (400 MHz, Acetone-d6): δ ppm 8.65 (br. s., 1H), 8.57 (d, 1H), 7.63 (t, 1H), 7.46-7.53 (m, 1H), 7.41-7.46 (m, 1H), 7.35-7.41 (m, 2H), 6.99 (d, 1H), 4.69 (d, 2H). LCMS m/z 405.9 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08304419B2
Source dataset	uspto-grants-2012_11
ORD ID	ord-7304729ef5ef4e3a8dff57d7e70f8e84
Source note	uspto-grants-2012_11