4-Methylmorpholine → 2-Bromo-5-(3-chloro-4-fluoro-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

https://huagongshe.com/reaction/2204296

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
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	5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid	HCID 86703099	—
Solvent	Ethyl Acetate	HCID 8857	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-Bromo-5-(3-chloro-4-fluoro-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one	HCID 86703098	—

Reaction Conditions

Temperature	80 °C

Reaction Steps

A mixture of 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid (Step D1) (1.483 mmol), HATU (1.632 mmol) and NMM (4.45 mmol) in dioxane (75 mL) was heated at 80° C. for 17 h. After cooling to rt, the reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with EtOAc (2×). The combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a light-yellow solid. tR: 5.31 min (HPLC 2); ESI-MS: tR=1.40 min, [M+H]+481/483/485 (LC-MS 1); TLC: Rf=0.27 (1:3 EtOAc/hexanes).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09365576B2
Source dataset	uspto-grants-2016_06
ORD ID	ord-90566a1bd14744df8e339bf9c173255d
Source note	uspto-grants-2016_06