HCID 67116992, compound → HCID 52911612, compound

HRID 69565Notes

Reaction equation

[Cl:1][C:2]([F:13])([F:12])[CH2:3][CH:4]1[CH2:8][N:7]([CH2:9]Cl)[C:6](=[O:11])[CH2:5]1.C([O:21][CH2:22][C:23]1[S:27][C:26]2=[N:28][C:29]([C:31]([F:34])([F:33])[F:32])=[CH:30][N:25]2[N:24]=1)C1C=CC=CC=1>O1CCOCC1.FC(F)(F)C(O)=O.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]([F:13])([F:12])[CH2:3][CH:4]1[CH2:8][N:7]([CH2:9][C:30]2[N:25]3[C:26]([S:27][C:23]([CH2:22][OH:21])=[N:24]3)=[N:28][C:29]=2[C:31]([F:33])([F:34])[F:32])[C:6](=[O:11])[CH2:5]1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 4-(2-chloro-2,2-difluoroethyl)-1-(chloromethyl)pyrrolidin-2-one a18 in dioxane (5 ml) is added to a hot solution (90° C.) of dry ZnCl2 (0.272 g, 2 mmol, 0.5 eq) and 2-[(benzyloxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a29 (1.3 g, 4 mmol, 1 eq) in dioxane (5 ml). The reaction mixture is heated at 90° C. for 3 days and 1,4-dioxane is removed under reduced pressure. The crude reaction mixture is taken up in trifluoroacetic acid (20 ml) and heated at 60° C. for 2 hours. After cooling, the trifluoro-acetic acid is removed under reduced pressure. The residue is purified by chromatography on silicagel (MeOH/CH2Cl2) and pure 4-(2-chloro-2,2-difluoroethyl)-1-{[2-(hydroxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one 7 (573 mg) is obtained after re-crystallization from ethyl acetate.

Workup

custom1,4-dioxane is removed under reduced pressure
customThe crude reaction mixture
temperatureheated at 60° C. for 2 hours
temperatureAfter cooling
customthe trifluoro-acetic acid is removed under reduced pressure
customThe residue is purified by chromatography on silicagel (MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-e01aac73634f42ffb278b1f54fc579c6
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822508B2

Reaction notes

Loading…