Methanol → 1-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(4,5-dimethyl-6-(2-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 869944Notes

Reaction equation

HRID 869944 reaction equation
[F:1][C:2]1([F:34])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([CH3:31])=[N:25][C:26]([O:29]C)=[CH:27][CH:28]=5)[C:20]([CH3:32])=[C:19]([CH3:33])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[Si](I)(C)(C)C.CO.C(OCC)(=O)C>CC#N>[F:34][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH3:33])[C:20]([CH3:32])=[C:21]([C:23]5[CH:28]=[CH:27][C:26](=[O:29])[NH:25][C:24]=5[CH3:31])[N:22]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 85247Trimethylsilyl iodideHCID 710530381-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6'-methoxy-2',3,4-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 710530721-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(4,5-dimethyl-6-(2-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamideYield 74%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-2′,3,4-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (41.6 mg, 0.09 mmol) in CH3CN (1.8 mL) was added TMSI (25.3 μL, 0.18 mmol) drop wise. The suspension became clear solution on TMSI addition. The reaction was stirred at 55° C. for 2 hours and 30 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×), 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-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4,5-dimethyl-6-(2-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide as a white solid (30 mg, 74%). ESI-MS m/z calc. 453.4. found 454.3 (M+1)+. Retention time 1.50 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-058048705793456784b4c3dfcda8bc4c
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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