Pyrrolidine → 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)-1-(pyrrolidin-1-yl)ethanone

Participants

Role	Name	HCID	Charge
Reactant	Pyrrolidine	HCID 31268	—
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	2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid	HCID 66575782	—
Solvent	Dichloromethane	HCID 6344	—
Product	2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)-1-(pyrrolidin-1-yl)ethanone	HCID 66575781	28.2%

Reaction Steps

To a suspension of 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid (510 mg, 1.4 mmol) in CH2Cl2 (9 mL) were added pyrrolidine (174 μL, 2.1 mmol), diisopropylethylamine (DIPEA) (366 μL, 2.1 mmol) and 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (798 mg, 2.1 mmol). The solution obtained was stirred at room temperature for 90 min then diluted with CH2Cl2. The organic phase was washed with aqueous NaHCO3, passed over a phase separator and concentrated in vacuo. The resultant residue was purified using chromatography (silica gel, gradient 0 to 70% ethyl acetate/isohexane) followed by a second chromatography purification (silica gel, gradient 0 to 25% dichloromethane/ether) yielding Compound 45 as a solid (165 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09260381B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-d228103f0ce4433c8a48fcad89cf4f7a
Source note	uspto-grants-2016_02