Methanol → HCID 25118721, compound

HRID 869930Notes

Reaction equation

HRID 869930 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([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])=[CH:18][CH:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[Si](I)(C)(C)C.CO.C(OCC)(=O)C>CC#N>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[CH:18][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:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 85247Trimethylsilyl iodide2×HCID 68739156HCID 68739156, compound

Product 1

HCID 25118721HCID 25118721, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 1-(2,3-dihydro-1H-inden-5-yl)-N-(6′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (0.127 g, 0.3172 mmol) in CH3CN (6.7 mL) was added TMSI (254 mg, 180.5 μL, 1.27 mmol) drop-wise. The suspension became a clear solution upon TMSI addition. The reaction was stirred at 55° C. for 6.5 hours. The reaction was allowed to cool down to room temperature. Methanol (2.0 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-dihydro-1H-inden-5-yl)-N-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide as a yellow solid (0.096 g, 78.5%). ESI-MS m/z calc. 385.46. found 386.5 (M+1)+. Retention time 1.58 minutes.

Workup

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

Sources & evidence

ORD record
ord-5e23f554dfbc4f1fa3e25cab0edb681a
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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