Methanol → HCID 25118722, compound

HRID 869950Notes

Reaction equation

HRID 869950 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:23]=[N:24][C:25]([O:28]C)=[CH:26][CH:27]=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][C:25](=[O:28])[NH:24][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 iodide2×HCID 68723140HCID 68723140, compound

Product 1

HCID 25118722HCID 25118722, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 1-(2,3-dihydrobenzofuran-5-yl)-N-(6′-methoxy-3,4-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (100 mg, 0.24 mmol) in CH3CN (4.75 mL) was added TMSI (68.4 μL, 0.48 mmol) drop wise. The reaction was stirred at 55° C. After 65 minutes, mainly starting material and some product observed. Two more equivalents of TMSI were added and the heating at 55° C. was continued for 3 hours 20 minutes. 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×: until the yellow colour disappeared), 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-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide as a white solid (60 mg, 62%). ESI-MS m/z calc. 401.5. found 402.3 (M+1)+. Retention time 1.33 minutes.

Workup

  1. waitthe heating at 55° C. was continued for 3 hours 20 minutes
  2. temperatureto cool down to room temperature
  3. washThe organic layer was washed with NaHSO3 (2×
  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-f5b167d5a2d44816b0bfe5464bd6f46c
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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