Imidazole → 8-(4-{[tert-Butyl(dimethyl)silyl]oxy}piperidin-1-yl)-5-chloro-N-methoxy-N-methylquinoline-7-carboxamide

HRID 1192532Notes

Reaction equation

HRID 1192532 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13])[C:9]([N:18]2[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.N1C=CN=C1.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>CN(C)C=O>[Si:30]([O:24][CH:21]1[CH2:20][CH2:19][N:18]([C:9]2[C:10]([C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13])=[CH:11][C:2]([Cl:1])=[C:3]3[C:8]=2[N:7]=[CH:6][CH:5]=[CH:4]3)[CH2:23][CH2:22]1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 583684265-chloro-8-(4-hydroxypiperidin-1-yl)-N-methoxy-N-methylquinoline-7-carboxamide

Product 1

HCID 583685548-(4-{[tert-Butyl(dimethyl)silyl]oxy}piperidin-1-yl)-5-chloro-N-methoxy-N-methylquinoline-7-carboxamideYield 63.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-chloro-8-(4-hydroxypiperidin-1-yl)-N-methoxy-N-methylquinoline-7-carboxamide (372 mg, 1.06 mmol) and 1H-imidazole (0.362 g, 5.32 mmol) in N,N-dimethylformamide (2 mL) was added tert-butyldimethylsilyl chloride (0.240 g, 1.60 mmol). The reaction was stirred at room temperature overnight, then quenched with sat. sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulfate and evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 40% ethyl acetate in hexane, to give the desired product (0.312 g, 63%). LCMS calculated for C23H35ClN3O3Si (M+H)+: m/z=464.2; Found: 464.2.

Workup

  1. customquenched with sat. sodium bicarbonate
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe residue was purified on silica gel
  7. washeluting with 0 to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-49d41fc7c1be4d669dfdea50922bbf17
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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