5-chloro-N-methoxy-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-N-methylquinoline-7-carboxamide → 1-{5-chloro-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-7-yl}ethanone

HRID 1192504Notes

Reaction equation

HRID 1192504 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12](N(OC)C)=[O:13])[C:9]([N:18]2[CH2:22][CH2:21][CH2:20][C@@H:19]2[CH2:23][O:24][CH3:25])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:26][Mg]Br>O1CCCC1>[Cl:1][C:2]1[CH:11]=[C:10]([C:12](=[O:13])[CH3:26])[C:9]([N:18]2[CH2:22][CH2:21][CH2:20][C@@H:19]2[CH2:23][O:24][CH3:25])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

4

Reactant 2

HCID 866561785-chloro-N-methoxy-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-N-methylquinoline-7-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 673016501-{5-chloro-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-7-yl}ethanoneYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 5-chloro-N-methoxy-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-N-methylquinoline-7-carboxamide (132 mg, 0.363 mmol) in tetrahydrofuran (0.5 mL) was added 1.40 M methylmagnesium bromide in tetrahydrofuran (1.6 mL, 2.2 mmol). The reaction was stirred at room temperature overnight, quenched with saturated ammonium chloride, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, then concentrated to dryness under reduced pressure. The resultant residue was purified on silica gel, eluting with 0 to 10% methanol in dichloromethane, to give the desired product (14 mg, 12%). LCMS calculated for C17H20ClN2O2(M+H)+: m/z=319.1; found: 319.1.

Workup

  1. customquenched with saturated ammonium chloride
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe resultant residue was purified on silica gel
  7. washeluting with 0 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-a76ac101209543538a3915c05de1bffd
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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