Dimethylformamide → Trifluoroacetic acid

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	4-Methylmorpholine	HCID 7972	—
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-(Aminomethyl)-1,3-thiazol-2-amine	HCID 22401521	—
Reactant	2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid	HCID 67458957	—
Product	Trifluoroacetic acid	HCID 6422	17.4%
Product	HCID 53496093	HCID 53496093	—

Reaction Steps

(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 30 mg, 0.070 mmol), 4-(aminomethyl)thiazol-2-amine (13.48 mg, 0.104 mmol), 4-methylmorpholine (28.1 mg, 0.278 mmol), and HATU (34.4 mg, 0.090 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention=11.4 min) to provide (R/S)-N-((2-aminothiazol-4-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide, TFA (10 mg, 0.012 mmol, 17.4% yield): LCMS=543.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.18 (2 H, d, J=8.36 Hz), 7.53-7.78 (7 H, m), 6.54 (1 H, s), 5.21 (1 H, s), 4.32(2 H, s); HPLC peak RT=8.1 min (Method A).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08835470B2
Source dataset	uspto-grants-2014_09
ORD ID	ord-563b03dd3c9244afa4da4904bac157cf
Source note	uspto-grants-2014_09