1,4-Dioxane → 1-(1-(5,6-dimethylpyrazin-2-yl)piperidin-4-yl)-N,N-dimethyl-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	1,4-Dioxane	HCID 31275	—
Reactant	5-Chloro-2,3-dimethylpyrazine	HCID 12600390	—
Reactant	Sodium t-butoxide	HCID 23676156	—
Reactant	N,N-dimethyl-1-(piperidin-4-yl)-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide	HCID 24798103	—
Catalyst	Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)	HCID 11029508	—
Solvent	Acetonitrile	HCID 6342	—
Product	1-(1-(5,6-dimethylpyrazin-2-yl)piperidin-4-yl)-N,N-dimethyl-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide	HCID 23651710	—

Reaction Conditions

Temperature	80 °C

Reaction Steps

Pd2(dba)3-CHCl3 (5 mg, 0.5 mol %), ligand 1 (8 mg, 2 mol %) and 1.4 eq sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into a microwave tube, followed by dioxane (750 μL), 1.0 eq N,N-dimethyl-1-(piperidin-4-yl)-2′H-spiro[piperidine-4,4′-quinoline]-1′(3′H)-carboxamide (36 mg, 0.10 mmol) and 1.0 eq 5-chloro-2,3-dimethylpyrazine (14 mg). The tube was flushed with nitrogen, capped and stirred at 80° C. for 3 hours. The reaction was cooled to room temperature, diluted with methanol (500 μL), filtered (Whatman 0.45 μm PTFE) and subjected to reverse-phase HPLC purification (2-40% CH3CN gradient [w/0.1% TFA (aq)] over t=10 minutes, 750 μL injected, 35 mL/min) to yield compound no. 20. LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 463.4, retention time 2.13 minutes.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08263605B2
Source dataset	uspto-grants-2012_09
ORD ID	ord-73f0c82dd4c8472d9903265ffd7f2dc5
Source note	uspto-grants-2012_09