4-Cyano-N-(2-(4,4-dimethylcyclohex-1-en-1-yl)-6-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamide → HCID 178424627, compound

HRID 456008Notes

Reaction equation

HRID 456008 reaction equation
[CH3:1][C:2]1([CH3:42])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH:14][C:15]([C:17]3[N:18](COCC[Si](C)(C)C)[CH:19]=[C:20]([C:22]#[N:23])[N:21]=3)=[O:16])=[CH:12][CH:11]=[C:10]([CH:32]3[CH2:37][C:36]([CH3:39])([CH3:38])[O:35][C:34]([CH3:41])([CH3:40])[CH2:33]3)[N:9]=2)=[CH:4][CH2:3]1>CN(C=O)C>[CH3:1][C:2]1([CH3:42])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH:14][C:15]([C:17]3[NH:18][CH:19]=[C:20]([C:22]#[N:23])[N:21]=3)=[O:16])=[CH:12][CH:11]=[C:10]([CH:32]3[CH2:33][C:34]([CH3:41])([CH3:40])[O:35][C:36]([CH3:39])([CH3:38])[CH2:37]3)[N:9]=2)=[CH:4][CH2:3]1

Participants

3

Reactant 1

HCID 576665694-Cyano-N-(2-(4,4-dimethylcyclohex-1-en-1-yl)-6-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamide

Product 1

HCID 178424627HCID 178424627, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid[2-(4,4-dimethyl-cyclohex-1-enyl)-6-(2,2,6,6-tetramethyl-tetrahydro-pyran-4-yl)-pyridin-3-yl]-amide (as prepared in the previous example, 17.6 g, 0.0290 mol) in DMF (30 mL) was added solid TBAF hydrate (16.6 g, 0.0630 mol ). The resulting mixture was heated at 70° C. overnight. The reaction mixture was allowed to cool to RT and partitioned between EtOAc (200 mL) and water (200 mL). The organic layer was separated, the aqueous layer was washed with EtOAc (3×100 mL) and the organic layers were combined, dried (Na2SO4) and concentrated. The resulting residue was dried under high vacuum to remove residual DMF. The residue was purified on silica gel (0-50% EtOAc/hexane). The resulting solid was then suspended in 25% ether/hexane and sonicated for 10 min. The product was collected by suction filtration and dried in a vacuum oven at 60° C. for 12 h to obtain the title compound as a white solid (10.2 g, 75%.) 1H-NMR (DMSO; 400 MHz): δ 14.26 (s, 1H), 10.02 (s, 1H), 8.32 (s, 1H), 8.12 (d, 1H, J=8.3 Hz), 7.24 (d, 1H, J=8.3 Hz), 5.86 (br s, 1H), 3.23 (m, 1H), 2.40 (m, 2H), 1.91 (m, 2H), 1.74 (dd, 2H, J=12.9, 3.3 Hz), 1.48 (m, 4H), 1.30 (s, 6H), 1.15 (s, 6H), 0.96 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H35N5O2, 462.2 (M+H), found 462.3.

Workup

  1. temperatureto cool to RT
  2. custompartitioned between EtOAc (200 mL) and water (200 mL)
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed with EtOAc (3×100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe resulting residue was dried under high vacuum
  8. customto remove residual DMF
  9. customThe residue was purified on silica gel (0-50% EtOAc/hexane)
  10. customsonicated for 10 min
  11. filtrationThe product was collected by suction filtration
  12. customdried in a vacuum oven at 60° C. for 12 h

Sources & evidence

ORD record
ord-4d39462e8ab04e30b5738b09bfc6fc50
Source dataset
uspto-grants-2013_07
Patent number
US08497376B2

Reaction notes

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