Methyl 4-aminopyridine-2-carboxylate → 4-(4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)benzamido)picolinic Acid

Participants

Role	Name	HCID	Charge
Reactant	Methyl 4-aminopyridine-2-carboxylate	HCID 3759117	—
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	4,5-Dichloro-2-(4-fluoro-2-methoxyphenoxy)benzoic acid	HCID 90314379	—
Catalyst	Sodium Hydroxide	HCID 14798	—
Solvent	Dimethylformamide	HCID 6228	—
Product	4-(4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)benzamido)picolinic Acid	HCID 90315453	7%

Reaction Conditions

Temperature	50 °C

Reaction Steps

4,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoic acid (40 mg, 0.12 mmol), methyl 4-aminopicolinate (36.5 mg, 0.24 mmol) and HATU (45.9 mg, 0.12 mmol) were combined in DMF (1 mL) and heated at 50° c. for 2 hours. The reaction was treated with 10 drops of 3 M NaOH and heated at 50° C. for 16 h. The reaction was filtered and purified by reverse phase HPLC using a gradient of acetonitrile in water containing HCl (5 mM) as a modifier (10-99%) to yield 4-(4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)benzamido)picolinic acid (76) (3.80 mg, 7%). ESI-MS m/z calc. 450.02, found 451.1 (M+1)+; Retention time: 1.47 minutes (3 minutes run).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09108903B2
Source dataset	uspto-grants-2015_08
ORD ID	ord-e133735061df45b5a7dec9d5febd4b4e
Source note	uspto-grants-2015_08