Imidazole → HCID 67006822, compound

HRID 2388429Notes

Reaction equation

HRID 2388429 reaction equation
[Cl:1][C:2]1[C:3]([CH3:28])=[C:4]([NH:10][C@H:11]([C@@H:25]([OH:27])[CH3:26])[C:12]([NH:14][NH:15][C:16](=[O:24])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:29][C:30]([Si:33](Cl)([CH3:35])[CH3:34])([CH3:32])[CH3:31].N1C=CN=C1>>[Si:33]([O:27][C@@H:25]([CH3:26])[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[CH3:28])[C:12]([NH:14][NH:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)=[O:13])([C:30]([CH3:32])([CH3:31])[CH3:29])([CH3:35])[CH3:34]

Participants

4

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006043HCID 67006043, compound

Product 1

HCID 67006822HCID 67006822, compound

Procedure

N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-fluoro benzohydrazide (15.2 g, 38.0 mmol) was protected using TBDMSCl (11.32 g, 75.0 mmol) and imidazole (10.23 g, 150 mmol) in a manner analogous to that described for the preparation of intermediate 7b. Purification of the compound was accomplished by pouring the reaction mixture into ice-cold water (1.6 L) and filtering off the solid precipitate. This was taken up in methylene chloride (700 mL) and sequentially washed with water (2×200 mL) and brine (1×200 mL). This was then dried over sodium sulfate, filtered and concentrated down to give a yellow solid. After column chromatography (50% EtOAc/hexanes) the title compound was isolated as a white solid (20 g, quant.). 1H NMR (400 MHz, CDCl3, δ in ppm) 9.32 (m, 2H), 7.77 (dd, J=5.3, 8.8 Hz, 2H), 7.27 (d, J=8.7 Hz, 1H), 7.05 (t, J=8.6 Hz, 2H), 6.54 (d, J=8.7 Hz, 1H), 4.94 (d, J=6.0 Hz, 1H), 4.36 (m, 1H), 4.01 (t, J=5.3 Hz, 1H), 2.26 (s, 3H), 1.35 (d, J=6.4 Hz, 3H), 0.89 (s, 9H), 0.14 (s, 3H), 0.09 (s, 3H).

Workup

  1. customPurification of the compound
  2. additionby pouring the reaction mixture into ice-cold water (1.6 L)
  3. filtrationfiltering off the solid precipitate
  4. washsequentially washed with water (2×200 mL) and brine (1×200 mL)
  5. dry with materialThis was then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customto give a yellow solid

Sources & evidence

ORD record
ord-a93aed890fe14f0ca66cad4b74eed386
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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