Hydrochloric Acid → N2-((4-chloro-1H-benzo[d]imidazol-5-yl)methyl)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-methylpyrimidine-2,4-diamine

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	2-chloro-N-(3-cyclopropyl-1H-pyrazol-5-yl)-5-fluoropyrimidin-4-amine	HCID 58169306	—
Reactant	1-(4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)-N-methylmethanamine	HCID 71272192	—
Solvent	1-Butanol	HCID 263	—
Product	N2-((4-chloro-1H-benzo[d]imidazol-5-yl)methyl)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-methylpyrimidine-2,4-diamine	HCID 71528974	—

Reaction Conditions

Temperature	120 °C

Reaction Steps

A vial was charged with 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoropyrimidin-4-amine (55, 95 mg, 0.37 mmol, CASRN 854434-98-5), the bis-HCl salt of 220 (185 mg, 0.52 mmol), DIPEA (0.33 mL) and n-BuOH (0.8 mL), sealed and heated at 120° C. for 96 h. The reaction mixture was concentrated in vacuo. The crude mixture was purified by preparative HPLC to afford 93.2 mg (60%) of I-86: MS (ESI) m/z=413.1 [M+1]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08637537B2
Source dataset	uspto-grants-2014_01
ORD ID	ord-73b404a61bf54380b08d584325c1aef0
Source note	uspto-grants-2014_01