HCID 117840299, compound → HCID 117840684, compound

HRID 714919Notes

Reaction equation

HRID 714919 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C@@H:11]([CH2:13][CH3:14])[C@:10]([CH:17]3[CH2:19][CH2:18]3)([C:15]#[N:16])[C:9]2=[O:20])[CH:5]=[CH:4][N:3]=1.ClC1N=C(N2CC(CC)C(C3CC3)(C#N)C2=O)C=CN=1>CCCCCC.CC(O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C@@H:11]([CH2:13][CH3:14])[C@@:10]([CH:17]3[CH2:19][CH2:18]3)([C:15]#[N:16])[C:9]2=[O:20])[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 117840299HCID 117840299, compoundHCID 117841110HCID 117841110, compound

Product 1

HCID 117840684HCID 117840684, compoundYield 109.8%

Reagents, catalysts & solvents 1

HCID 21585144Isopropanol hexaneSolvent

Procedure

To a mixture of 3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (3.7 g) obtained in Step B of Example 376, 2,4-dichloropyrimidine (3.1 g), cesium carbonate (13 g) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.71 g) in tetrahydrofuran (55 mL) was added tris(dibenzylideneacetone)dipalladium(0) (0.38 g), and the mixture was stirred overnight at 85° C. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give (3SR,4RS)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (1.3 g) and (3SR,4SR)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (1.6 g). (3SR,4RS)-1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (1.3 g) was resolved by HPLC (column: CHIRALCEL OD, 50 mmID×500 mmL, manufactured by Daicel Chemical Industries, mobile phase: hexane/2-propanol=700/300) to give (3S,4R)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (500 mg) having a shorter retention time and (3R,4S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (510 mg) having a longer retention time. (3SR,4SR)-1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (1.6 g) was resolved by HPLC (column: CHIRALCEL OD, 50 mmID×500 mmL, manufactured by Daicel Chemical Industries, mobile phase: hexane/2-propanol=700/300) to give (3S,4S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (560 mg) having a shorter retention time and (3R,4R)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-ethyl-2-oxopyrrolidine-3-carbonitrile (600 mg) having a longer retention time.

Sources & evidence

ORD record
ord-22b7c582ddc649a4b5b5428623d7cd1d
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…