Dichloromethane → (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxy-2-methylpropoxy)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide

HRID 2192943Notes

Reaction equation

HRID 2192943 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:41][C@H:42]3[CH2:46][CH2:45][C:44](=[O:47])[CH2:43]3)[C:17]([NH:19][C:20]3[CH:25]=[N:24][C:23]([O:26][CH2:27][C:28]([O:31]CC4C=CC(OC)=CC=4)([CH3:30])[CH3:29])=[CH:22][N:21]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.ClCCl>O>[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:41][C@H:42]3[CH2:46][CH2:45][C:44](=[O:47])[CH2:43]3)[C:17]([NH:19][C:20]3[CH:25]=[N:24][C:23]([O:26][CH2:27][C:28]([OH:31])([CH3:29])[CH3:30])=[CH:22][N:21]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 68671583(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide

Product 1

HCID 44199003(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxy-2-methylpropoxy)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamideYield 77.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acid (99 mg) in dichloromethane (2.0 mL) were added oxalyl chloride (27 μL) and DMF (3 μL) under ice-cooling, followed by stirring for 10 minutes. Thereafter, pyridine (28 μL) and 5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-amide (53 mg) were added thereto under ice-cooling, followed by stirring for 20 minutes. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide (82 mg) as a white amorphous substance. A mixture of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide (82 mg), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (56 mg), dichloromethane (7.5 mL), and water (0.38 mL) was stirred at room temperature for 10 minutes. To the reaction mixture was added water, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=80:20). The obtained residue was sonicated with diethyl ether and the resulting precipitate was collected by filtration to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxy-2-methylpropoxy)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide (52 mg) as a white solid.

Workup

  1. extractionfollowed by extraction with chloroform
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customThe solvent was evaporated
  4. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=80:20)
  5. customThe obtained residue was sonicated with diethyl ether
  6. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-180d938148024fff821566463c41e82d
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

Loading…