Diisopropylethylamine → HCID 178502459, compound

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
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	(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid	HCID 59264488	—
Reactant	N-{5-chloro-4'-[2-((2S,4S)-4-methoxy-pyrrolidin-2-yl)-1H-imidazol-4-yl]-2-trifluoromethoxy-biphenyl-4-yl}-6-[(R)-4-(2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide tri-HCl	HCID 178496717	—
Solvent	Dimethylacetamide	HCID 31374	—
Product	HCID 178502459	HCID 178502459	68.4%

Reaction Steps

To a solution of (S)-methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (9.4 mg, 0.046 mmol; Preparation 29) in DMA (1 mL) was added HATU (6.4 mg, 0.017 mmol). The reaction mixture was stirred at RT for 15 min, and N-{5-chloro-4′-[2-((2S,4S)-4-methoxy-pyrrolidin-2-yl)-1H-imidazol-4-yl]-2-trifluoromethoxy-biphenyl-4-yl}-6-[(R)-4-(2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide tri-HCl (12.0 mg, 0.014 mmol; Preparation 32) was added followed by DIPEA (12.3 μL, 0.07 mmol). The reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (1.5 mL) and purified by reverse phase HPLC to provide the di-TFA salt of the title compound (9 mg, 56% yield). (m/z): [M+H]+ calcd for C46H54ClF3N8O8 939.37. found 939.8.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09212168B2
Source dataset	uspto-grants-2015_12
ORD ID	ord-ea6242f9a8624b80a21763c59d5a70a6
Source note	uspto-grants-2015_12