Imidazole → HCID 59193079, compound

HRID 470915Notes

Reaction equation

HRID 470915 reaction equation
[Cl:1][C:2]1[C:3]([CH3:30])=[C:4]([NH:10][C@H:11]([C@@H:27]([OH:29])[CH3:28])[C:12]([NH:14][NH:15][C:16]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][CH:22]=[CH:21]3)=[O:17])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CN(C=O)C.N1C=CN=C1.[C:41]([Si:45](Cl)([CH3:47])[CH3:46])([CH3:44])([CH3:43])[CH3:42]>CCOC(C)=O.O>[Si:45]([O:29][C@@H:27]([CH3:28])[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[CH3:30])[C:12]([NH:14][NH:15][C:16]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[CH:21]2)=[O:17])=[O:13])([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:47])[CH3:46]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 59193078HCID 59193078, compound

Product 1

HCID 59193079HCID 59193079, compoundYield 186%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 500 mL round bottomed flask was charged with N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-1H-indole-5-carbohydrazide (1.94 g, 4.56 mmol) and DMF (200 mL). Imidazole (1.55 g, 22.78 mmol) and tert-butyldimethyl silyl chloride (2.06 g, 13.68 mmol) were then added to the mixture which was stirred at room temperature for 18 h. Water (80 mL) was added to the mixture followed by EtOAc (150 mL). The phases were partitioned and the organic phase washed with water (70 mL) (×4), brine (50 mL), dried (Na2SO4) and concentrated to furnish a white solid. Purification by flash column chromatography [EtOAc-hexanes) as eluent] afforded the title compound as a colorless oil (4.58 g, 35% yield). 1H NMR (500 MHz, acetone d6, δ in ppm) δ 10.51 (br s, 1H), 9.5 (br s, 1H), 8.22 (br s, 1 H), 7.70 (d, J=8.41 Hz, 1H), 7.55-7.47 (m, 2 H), 7.44-7.42 (m, 1H), 6.77 (d, J=8.6 Hz, 1 H), 6.58-6.56 (m, 1H), 5.51 (d, J=7 Hz), 4.63-4.55 (m, 1H), 4.23-4.19 (m, 1H), 2.36 (s, 3H) and 1.36 (d, J=6.23 Hz, 3H), 0.95 (s, 9 H), 0.17 (s, 3 H) and 0.13 (s, 3H).

Workup

  1. customThe phases were partitioned
  2. washthe organic phase washed with water (70 mL) (×4), brine (50 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customto furnish a white solid
  6. customPurification by flash column chromatography [EtOAc-hexanes) as eluent]

Sources & evidence

ORD record
ord-00ae981a6e8547e5b43b0e232f264334
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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