Trimethylsilyl iodide → 1-(2,3-Dihydrobenzofuran-5-yl)-n-(5-methyl-6-(2-oxo-1,2-dihydropyridin-4-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 869989Notes

Reaction equation

HRID 869989 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])=[CH:18][CH:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.I[Si](C)(C)C>C(Cl)(Cl)Cl>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([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][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

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 687211511-(2,3-Dihydrobenzofuran-5-yl)-n-(2'-methoxy-3-methyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 251187201-(2,3-Dihydrobenzofuran-5-yl)-n-(5-methyl-6-(2-oxo-1,2-dihydropyridin-4-yl)pyridin-2-yl)cyclopropanecarboxamideYield 36.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

To 1-(2,3-dihydrobenzofuran-5-yl)-N-(2′-methoxy-3-methyl-2,4′-bipyridin-6-yl)cyclopropanecarboxamide (42 mg, 0.1 mmol) in chloroform (2 mL) was added iodotrimethylsilane (63 mg, 0.3 mmol). The reaction mixture was heated to 60° C. for one hour. The reaction was evaporated to dryness and the residue was dissolved in N,N-dimethylformamide (1 mL) and purified by reverse-phase preparative liquid chromatography. The resulting trifluoroacetic acid salt was dissolved in dichloromethane (5 mL) and washed with a saturated sodium bicarbonate solution (5 mL). The organics were dried over sodium sulfate and evaporated to dryness to yield the product (14 mg, 36%) ESI-MS m/z calc. 387.43. found 388.5 (M+1)+. Retention time 1.41 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.19 (s, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.40-7.37 (m, 2H), 7.26-7.24 (m, 1H), 6.80 (d, J=8.2 Hz, 1H), 6.28 (m, 1H), 6.18-6.15 (m, 1H), 4.55 (t, J=8.7 Hz, 2H), 3.19 (t, J=8.6 Hz, 2H), 2.22 (s, 3H), 1.49-1.47 (m, 2H), 1.11-1.09 (m, 2H)

Workup

  1. customThe reaction was evaporated to dryness
  2. dissolutionthe residue was dissolved in N,N-dimethylformamide (1 mL)
  3. custompurified by reverse-phase preparative liquid chromatography
  4. dissolutionThe resulting trifluoroacetic acid salt was dissolved in dichloromethane (5 mL)
  5. washwashed with a saturated sodium bicarbonate solution (5 mL)
  6. dry with materialThe organics were dried over sodium sulfate
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-fe233ff4446a4bd482ca8a86d9ef43e6
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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