N-methyl-2-pyrrolidone → (1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

https://huagongshe.com/reaction/1965176

Participants

Role	Name	HCID	Charge
Reactant	N-methyl-2-pyrrolidone	HCID 13387	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Z-N-Me-Ala-OH	HCID 7016365	—
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-Amino-1-[6-(3,4-difluoro-phenoxy)-4-pyrimidin-2-yl-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-one	HCID 67505937	—
Product	(1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester	HCID 67608273	100%

Reaction Conditions

Temperature	0 °C

Reaction Steps

HATU (105 mg, 0.28 mmol) and Cbz-N(Me)Ala-OH (65 mg, 0.28 mmol) were dissolved in NMP (0.5 mL) and DIPEA (65 μL, 0.36 mmol) was added. The reaction mixture was cooled to 0° C. and a solution of 30 (106 mg, 0.25 mmol) in NMP (2 mL) was added. The reaction mixture was warmed to ambient temperature. After 12 h, the reaction mixture was quenched with 1N NaOH (0.5 mL) and diluted with water, extracted with 10:1 Et2O/EtOAc. The combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 180 mg (100%) of 31 as a beige-colored foam which was used without further purification. Mass spectrum, m/z [651.2] (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08415486B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-714609eaa61e48d396685b9d73b94b63
Source note	uspto-grants-2013_04