Methanol → HCID 68738229, compound

HRID 869952Notes

Reaction equation

HRID 869952 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[N:21]=[C:20]([C:22]5[CH:27]=[CH:26][N:25]=[C:24]([O:28]C)[CH:23]=5)[C:19]([CH3:30])=[C:18]([CH3:31])[CH:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.[Si](I)(C)(C)C.CO.C(OCC)(=O)C>CC#N>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]([CH3:31])[C:19]([CH3:30])=[C:20]([C:22]5[CH:27]=[CH:26][NH:25][C:24](=[O:28])[CH:23]=5)[N:21]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 85247Trimethylsilyl iodideHCID 68723216HCID 68723216, compound

Product 1

HCID 68738229HCID 68738229, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 1-(2,3-dihydrobenzofuran-5-yl)-N-(2′-methoxy-3,4-dimethyl-2,4′-bipyridin-6-yl)cyclopropanecarboxamide (96 mg, 0.23 mmol) in CH3CN (4.8 mL) was added TMSI (65.6 μL, 0.46 mmol) drop wise. The suspension became a clear solution on TMSI addition. The reaction was stirred at 55° C. for 5 hours. The reaction was allowed to cool down to room temperature. Methanol (1.0 mL) was added followed by ethyl acetate (6 mL). The organic layer was washed with NaHSO3 (2×), and brine (1×). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% methanol in dichloromethane) to yield 1-(2,3-dihydrobenzofuran-5-yl)-N-(4,5-dimethyl-6-(2-oxo-1,2-dihydropyridin-4-yl)pyridin-2-yl)cyclopropanecarboxamide as a white solid (50 mg, 54%). ESI-MS m/z calc. 401.5. found 402.5 (M+1)+. Retention time 1.41 minutes.

Workup

  1. additionon TMSI addition
  2. temperatureto cool down to room temperature
  3. washThe organic layer was washed with NaHSO3 (2×), and brine (1×)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel (0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-1af27de34acc425db397fb1ebc2f37a7
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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