Dimethylformamide → [(3RS,4SR)-3-[(RS)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(2-methyl-pyrimidin-5-yl)-methanone

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
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-{(RS)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine	HCID 67131726	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	[(3RS,4SR)-3-[(RS)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(2-methyl-pyrimidin-5-yl)-methanone	HCID 67131631	40%

Reaction Steps

To a solution of 2-{(RS)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine (8A-1) (220 mg) in DMF (12 mL) at −20° C. were added Hunig base (0.132 mL, 0.78 mmol) and then HATU (202 mg). The mixture was diluted with ethyl acetate and washed with aq.ammonium chloride solution three times and aq. sodium bicarbonate solution. The separated organic phase was dried over sodium sulfate and concentrated in vaccuo after filtration. The residue was purified by TLC (SiO2, MeOH/DCM, 1:20) yielded 24 mg (40%) of the title compound as a light yellow oil. ES-MS m/e: 623.1 M+H+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08012998B2
Source dataset	uspto-grants-2011_09
ORD ID	ord-0051038fa81f49f186dbd897a0e3913e
Source note	uspto-grants-2011_09