Trimethylsilyl iodide → N-(6-(3-chloro-2-oxo-1,2-dihydropyridin-4-yl)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 870002Notes

Reaction equation

HRID 870002 reaction equation
[Cl:1][C:2]1[C:3]([O:32]C)=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]([NH:15][C:16]([C:18]2([C:21]3[CH:31]=[CH:30][C:24]4[O:25][C:26]([F:29])([F:28])[O:27][C:23]=4[CH:22]=3)[CH2:20][CH2:19]2)=[O:17])[N:9]=1.I[Si](C)(C)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:3](=[O:32])[NH:4][CH:5]=[CH:6][C:7]=1[C:8]1[N:9]=[C:10]([NH:15][C:16]([C:18]2([C:21]3[CH:31]=[CH:30][C:24]4[O:25][C:26]([F:28])([F:29])[O:27][C:23]=4[CH:22]=3)[CH2:20][CH2:19]2)=[O:17])[CH:11]=[CH:12][C:13]=1[CH3:14]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 91096555N-(3'-chloro-2'-methoxy-3-methyl-2,4'-bipyridin-6-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Product 1

HCID 117640728N-(6-(3-chloro-2-oxo-1,2-dihydropyridin-4-yl)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To N-(3′-chloro-2′-methoxy-3-methyl-2,4′-bipyridin-6-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (71 mg, 0.15 mmol) in chloroform (2 mL) was added iodotrimethylsilane (90 mg, 0.45 mmol). The reaction mixture was stirred at room temperature for six hours. The reaction mixture was evaporated to dryness and purified by reverse phase preparative liquid chromatography to yield the product as a trifluoroacetic acid salt. The salt was dissolved in dichloromethane (5 mL) and washed with a saturated sodium bicarbonate solution (2×5 mL). The organics were dried over sodium sulfate and evaporated to yield the product (23 mg, 33%). ESI-MS m/z calc. 459.08. found 460.3 (M+1)+. Retention time 1.11 minutes. 1H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 9.11 (s, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.75 (d, J=8.6 Hz, 1H), 7.55 (m, 1H), 7.44 (d, J=6.6 Hz, 1H), 7.40-7.38 (m, 1H), 7.35-7.32 (m, 1H), 6.11 (d, J=6.6 Hz, 1H), 2.06 (s, 3H), 1.51-1.50 (m, 2H), 1.17-1.15 (m, 2H).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. custompurified by reverse phase preparative liquid chromatography

Sources & evidence

ORD record
ord-21bd8aaf4f6643d485c38150ec44eeaf
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

Loading…