Potassium Carbonate → 3-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]-N-methoxy-N-methylcyclobutane-1-carboxamide

HRID 511630Notes

Reaction equation

HRID 511630 reaction equation
[C:1]([C:5]1[CH:24]=[CH:23][C:8]2[NH:9][C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([C:17]([N:19]([O:21][CH3:22])[CH3:20])=[O:18])[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH3:31][Si:32]([CH3:39])([CH3:38])[CH2:33][CH2:34][O:35][CH2:36]Cl>CN(C)C=O>[C:1]([C:5]1[CH:24]=[CH:23][C:8]2[N:9]([CH2:36][O:35][CH2:34][CH2:33][Si:32]([CH3:39])([CH3:38])[CH3:31])[C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([C:17]([N:19]([O:21][CH3:22])[CH3:20])=[O:18])[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178502664HCID 178502664, compound

Product 1

HCID 866661233-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]-N-methoxy-N-methylcyclobutane-1-carboxamideYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-[(5-tert-butyl-1H-1,3-benzodiazol-2-yl)methyl]-N-methoxy-N-methylcyclobutane-1-carboxamide (80%, 2.02 g, 4.91 mmol) in N,N-dimethylformamide (40 ml) under N2 was added potassium carbonate (1.36 g, 9.81 mmol) and the reaction was stirred for 1 h. 2-(Trimethylsilyl)ethoxymethyl chloride (1.31 ml, 7.36 mmol) was added slowly, and stirring maintained for 20 h. The reaction mixture was filtered and concentrated under reduced pressure. The residue was taken up in EtOAc (50 ml) and washed with water (3×50 ml), then brine (50 ml) before being dried (MgSO4) and concentrated. The crude material was purified by silica flash column chromatography, eluting with 50-100% EtOAc in heptane to afford the title compound (1.21 g, 54%) as a colourless gum: MS (ESI+) for C25H41N3O3Si m/z 461.0 [M+H]+; LC purity 97% (UV), 100% (ELS), (ret. time, 1.98 min); 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.58-7.89 (m, 1H), 7.33 (s, 2H), 5.39-5.53 (m, 2H), 3.65 (s, 3H), 3.49-3.58 (m, 2H), 3.41 (br. s., 1H), 3.10-3.23 (m, 3H), 3.03 (s, 3H), 2.32-2.63 (m, 2H), 2.00-2.18 (m, 2H), 1.32-1.45 (m, 9H), 0.91 (td, J=8.1, 4.9 Hz, 2H), −0.13-0.07 (m, 9H).

Workup

  1. stirringstirring
  2. temperaturemaintained for 20 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. washwashed with water (3×50 ml)
  6. dry with materialbrine (50 ml) before being dried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude material was purified by silica flash column chromatography
  9. washeluting with 50-100% EtOAc in heptane

Sources & evidence

ORD record
ord-68b076079db84b78906b75e1c4dd3102
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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