Trifluoroacetic acid → 2-[6-Methoxy-5-(methylamino)pyridin-2-yl]-4-(2,4,6-trifluorobenzyl)-2H-pyrido[2,3-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide

Participants

Role	Name	HCID	Charge
Reactant	Trifluoroacetic acid	HCID 6422	—
Reactant	Triethylamine	HCID 8471	—
Reactant	1,1'-Carbonyldiimidazole	HCID 68263	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	2,4,6-Trifluorobenzylamine	HCID 2777046	—
Reactant	4-(2,6-Difluoro-4-methoxybenzyl)-2-[5-methoxy-6-(methylamino)pyridin-2-yl]-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide	HCID 72720880	—
Reactant	4-(2,6-difluoro-4-methoxybenzyl)-2-(3,4-dimethoxyphenyl)-2H-pyrido[2,3-e][1,2,4]thiadiazin-3 (4H)-one 1,1-dioxide	HCID 90054671	—
Reactant	tert-Butyl (6-{[(2-chloropyridin-3-yl)sulfonyl]amino}-2-methoxypyridin-3-yl)methylcarbamate	HCID 131734696	—
Solvent	Acetonitrile	HCID 6342	—
Solvent	Dichloromethane	HCID 6344	—
Product	2-[6-Methoxy-5-(methylamino)pyridin-2-yl]-4-(2,4,6-trifluorobenzyl)-2H-pyrido[2,3-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide	HCID 72720778	31.3%

Reaction Steps

The title compound (266 mg, 0.55 mmol) was prepared in three steps from tert-butyl(6-{[(2-chloropyridin-3-yl)sulfonyl]amino}-2-methoxypyridin-3-yl)methylcarbamate (IntC8) (755 mg, 1.76 mmol), 2,4,6-trifluorobenzylamine (1.13 g, 7.01 mmol) and N,N-diisopropylethylamine (0.46 mL, 2.64 mmol) in MeCN (10 mL) at 120° C. for 12 hours; followed by 1,1′-carbonyldiimidazole (832 mg, 5.13 mmol) and triethylamine (358 uL, 2.57 mmol) using the methods of (95); followed by TFA (2 mL) in DCM (3 mL) at rt using the method of (179), step 2.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09249160B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-8de1416011574adcb19e8b5b6c87ad45
Source note	uspto-grants-2016_02