HCID 117840235, compound → HCID 117840527, compound

HRID 714916Notes

Reaction equation

HRID 714916 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C@@H:11]([CH3:13])[C@:10]([CH:16]3[CH2:18][CH2:17]3)([C:14]#[N:15])[C:9]2=[O:19])[CH:5]=[CH:4][N:3]=1.ClC1N=C(N2CC(C)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]([CH3:13])[C@@:10]([CH:16]3[CH2:17][CH2:18]3)([C:14]#[N:15])[C:9]2=[O:19])[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 117840235HCID 117840235, compoundHCID 117840734HCID 117840734, compound

Product 1

HCID 117840527HCID 117840527, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 21585144Isopropanol hexaneSolvent

Procedure

1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (2.6 g) obtained in Step C of Example 357 was purified by silica gel column chromatography (hexane/ethyl acetate) to give (3SR,4RS)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (820 mg) and (3SR,4SR)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (1.3 g). (3SR,4RS)-1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (810 mg) was resolved by HPLC (column: CHIRALCEL OD, 50 mmID×500 mmL, manufactured by Daicel Chemical Industries, mobile phase: hexane/2-propanol=900/100) to give (3S,4R)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (400 mg) having a shorter retention time and (3R,4S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (400 mg) having a longer retention time. (3SR,4SR)-1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-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=900/100) to give (3S,4S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (400 mg) having a shorter retention time and (3R,4R)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-4-methyl-2-oxopyrrolidine-3-carbonitrile (400 mg) having a longer retention time.

Sources & evidence

ORD record
ord-34b4d1bb939645829ced81ea887e756c
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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