Morpholine → 5-Methyl-2-[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-7-morpholin-4-yl-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione

Participants

Role	Name	HCID	Charge
Reactant	Morpholine	HCID 8083	—
Reactant	Cesium carbonate	HCID 10796	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	7-Chloro-5-methyl-2-(2-(1-methyl-1H-benzo[D]imidazol-2-YL)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-C]pyridine-1,6(5H)-dione	HCID 71743596	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	5-Methyl-2-[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-7-morpholin-4-yl-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione	HCID 86296064	8.8%

Reaction Conditions

Temperature	120 °C

Reaction Steps

Palladium diacetate (189 mg, 0.841 mmol), Xantphos (486 mg, 0.841 mmol) and Cs2CO3 (822 mg, 2.52 mmol) were each rapidly added in sequence to a suspension of 7-chloro-5-methyl-2-[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (300 mg, 0.841 mmol, see Example c8)) and morpholine (220 mg, 2.52 mmol) in dioxane (1 ml). The reaction was heated in a microwave at about 120° C. for about 40 min. The solvent was removed and the resulting mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 10:90 to 35:65 over 15 min), column: Boston Analytics, C-18, 10 μm, 21×250 mm) to afford the title compound (30 mg, 0.074 mmol, 8.76% yield)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09163019B2
Source dataset	uspto-grants-2015_10
ORD ID	ord-b2ee1e073a054567bf55774cc7c20fae
Source note	uspto-grants-2015_10