Water → 4-(5-chloro-6-cyclopropylpyridin-3-yloxy)-3-(2-methoxypyridin-3-yl)-N-(methylsulfonyl)benzamide

HRID 1620316Notes

Reaction equation

HRID 1620316 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][C:13]=2[C:21]2[C:22]([O:27][CH3:28])=[N:23][CH:24]=[CH:25][CH:26]=2)[CH:5]=[N:6][C:7]=1[CH:8]1[CH2:10][CH2:9]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:39][S:40](Cl)(=[O:42])=[O:41].O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([NH:18][S:40]([CH3:39])(=[O:42])=[O:41])=[O:17])=[CH:14][C:13]=2[C:21]2[C:22]([O:27][CH3:28])=[N:23][CH:24]=[CH:25][CH:26]=2)[CH:5]=[N:6][C:7]=1[CH:8]1[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 666674084-(5-Chloro-6-cyclopropylpyridin-3-yloxy)-3-(2-methoxypyridin-3-yl)benzamide

Product 1

HCID 566029844-(5-chloro-6-cyclopropylpyridin-3-yloxy)-3-(2-methoxypyridin-3-yl)-N-(methylsulfonyl)benzamideYield 44.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(5-chloro-6-cyclopropylpyridin-3-yloxy)-3-(2-methoxypyridin-3-yl)benzamide (Preparation 40, 437 mg, 1.10 mmol) in anhydrous tetrahydrofuran (4 mL) under nitrogen was added 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (4.40 mL, 4.40 mmol). The solution was stirred 30 minutes at room temperature then methane sulfonyl chloride (340 μL, 4.40 mmol) was added and the reaction mixture was stirred 2 hours at room temperature. Water (50 mL) was added and the solution was extracted with ethyl acetate (3×20 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with Feb. 10, 1990 acetic acid/ethyl acetate/dichloromethane to afford the title compound as a white solid (230 mg, 44%).

Workup

  1. stirringthe reaction mixture was stirred 2 hours at room temperature
  2. extractionthe solution was extracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel column chromatography
  7. washeluting with Feb

Sources & evidence

ORD record
ord-21710ce45c3b4b5a9679b34be6e3e04d
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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