1,1'-Carbonyldiimidazole → 1-[(2S,3S)-2-[(tert-Butoxycarbonyl)amino]-3-[3-[2-chloro-4-[(methylsulfonyl)amino]phenyl]-1,2,4-oxadiazol-5-yl]-1-oxobutyl]pyrrolidine

HRID 2246243

Reaction equation

HRID 2246243 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15](=[O:21])[N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C@H:10]([CH3:14])[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:34][C:35]1[CH:40]=[C:39]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])[CH:38]=[CH:37][C:36]=1[C:46](=[N:48]O)[NH2:47]>ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:10]([C:11]1[O:13][N:48]=[C:46]([C:36]2[CH:37]=[CH:38][C:39]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:40][C:35]=2[Cl:34])[N:47]=1)[CH3:14])[C:15]([N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:21])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 68431373(2S,3S)-3-[(tert-Butoxycarbonyl)amino]-2-methyl-4-oxo-4-pyrrolidin-1-ylbutanoic acidHCID 725337992-Chloro-N'-hydroxy-4-[(methylsulfonyl)amino]benzenecarboximidamide2×

Product 1

HCID 684290061-[(2S,3S)-2-[(tert-Butoxycarbonyl)amino]-3-[3-[2-chloro-4-[(methylsulfonyl)amino]phenyl]-1,2,4-oxadiazol-5-yl]-1-oxobutyl]pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the product from Step B (132.0 mg, 0.44 mmol) in dichloromethane (5 mL) was added 1,1′-carbonyldiimidazole (148.0 mg, 0.91 mmol). After stirring at room temperature for 1 h, 2-chloro-N′-hydroxy-4-[(methylsulfonyl)amino]benzenecarboximidamide (Intermediate 6, 145.0 mg, 0.55 mmol) was added. After stirring at room temperature for 2 h, the reaction was quenched with saturated aqueous ammonium chloride solution. The organic phase was then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in 10 mL of toluene and heated at 110° C. for 12 h. The toluene was removed under reduced pressure and the residue was then purified by preparative thin layer chromatography (silica gel, 30:70 hexanes/ethyl acetate) to give the desired product.

Workup

  1. stirringAfter stirring at room temperature for 2 h
  2. customthe reaction was quenched with saturated aqueous ammonium chloride solution
  3. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 10 mL of toluene
  6. temperatureheated at 110° C. for 12 h
  7. customThe toluene was removed under reduced pressure
  8. customthe residue was then purified by preparative thin layer chromatography (silica gel, 30:70 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-daba1b9e1a96455395463ac052d1e63c
Source dataset
uspto-grants-2010_03
Patent number
US07687492B2

Linked notes

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