Imidazole → HCID 66625136, compound

HRID 238566Notes

Reaction equation

HRID 238566 reaction equation
[Cl:1][C:2]1[C:3]([CH2:29][CH2:30][CH3:31])=[C:4]([NH:10][C@H:11]([C@@H:26]([OH:28])[CH3:27])[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].C1COCC1.N1C=CN=C1.[C:42]([Si:46](Cl)([CH3:48])[CH3:47])([CH3:45])([CH3:44])[CH3:43]>CCOC(C)=O.CCCCCCC.O>[Si:46]([O:28][C@@H:26]([CH3:27])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH2:29][CH2:30][CH3:31])[C:12]([NH:14][NH:15][C:16](=[O:25])[C:17]1[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][CH:22]=1)=[O:13])([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:48])[CH3:47]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 8028TetrahydrofuranHCID 28928tert-Butyldimethylsilyl chlorideHCID 66624739HCID 66624739, compound2×

Product 1

HCID 66625136HCID 66625136, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

A 250 mL round bottom flask was charged with N′-((2R,3S)-2-(3-chloro-4-cyano-2-propylphenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide (intermediate 1119-B) (0.710 g, 1.61 mmol) and THF (20 mL) at room temperature. Imidazole (0.440 g, 6.47 mmol) and tert-butyldimethyl silyl chloride (0.730 g, 4.84 mmol) were then added to the mixture which was stirred at room temperature for 48 h. Water (20 mL) was then added to the mixture followed by heptane (50 mL) and stirred for 30 min at room temperature. EtOAc (50 mL) was then added and the phases were partitioned. The organic extract was separated, dried over Na2SO4, and concentrated to furnish a yellow solid. The crude material was purified by flash column chromatography [SiO2, EtOAc-hexanes (20%:80%)→EtOAc-hexanes (50%:50%)→EtOAc-hexanes (60%:40%) as eluent] to afford the title compound as a light yellow solid with other minor impurities (0.750 g, 84% yield), which was immediately taken to the next synthetic step.

Workup

  1. stirringstirred for 30 min at room temperature
  2. customthe phases were partitioned
  3. extractionThe organic extract
  4. customwas separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto furnish a yellow solid
  8. customThe crude material was purified by flash column chromatography [SiO2, EtOAc-hexanes (20%:80%)→EtOAc-hexanes (50%:50%)→EtOAc-hexanes (60%:40%) as eluent]

Sources & evidence

ORD record
ord-f1fdf74ddbbd4373869eb7f7b8b7af57
Source dataset
uspto-grants-2014_02
Patent number
US08642632B2

Reaction notes

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