p-Toluenesulfonic acid monohydrate → 1-(5-(4-((7R,8aS)-5,5-dimethyl-octahydroindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-methoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one

Participants

Role	Name	HCID	Charge
Reactant	p-Toluenesulfonic acid monohydrate	HCID 521998	—
Reactant	1-(5-Amino-4-fluoro-2-methoxyphenyl)-4-methyl-5H-tetrazol-5-one	HCID 58287208	—
Reactant	(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amine	HCID 86704490	—
Solvent	Isopropanol	HCID 3776	—
Product	1-(5-(4-((7R,8aS)-5,5-dimethyl-octahydroindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-methoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one	HCID 71811823	—

Reaction Conditions

Temperature	100 °C

Reaction Steps

A mixture of (7R,8aS)—N-(2-choro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (49 mg, 0.16 mmol, 1 equiv), 1-(5-amino-4-fluoro-2-methoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (59 mg, 0.25 mmol, 1.5 equiv) and pTsOH.H2O (25 mg, 0.13 mmol, 0.8 equiv) in isopropanol (1.5 ml) was heated at 100° C. overnight in a sealed vial. After allowing to cool to room temperature, the solvent was removed and the residue was purified by HPLC to give the product as a solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09169249B2
Source dataset	uspto-grants-2015_10
ORD ID	ord-884e13e9e69d4c41a885d18319fb5ff3
Source note	uspto-grants-2015_10