Cyclopropylamine → N-[3-({2-[(cyclopropylcarbamoyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-6-methylpyridine-2-carboxamide

HRID 1874550Notes

Reaction equation

HRID 1874550 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=4)=[O:19])[CH:14]=[CH:15][CH:16]=3)=[CH:6][N:5]2[CH:27]=1.C([N:31]([CH2:35]C)[CH:32]([CH3:34])[CH3:33])(C)C.ClC(Cl)(Cl)C[O:40]C(Cl)=O.C1(N)CC1>O1CCCC1.CN(C)C=O>[CH:32]1([NH:31][C:35]([NH:1][C:2]2[N:3]=[C:4]3[CH:9]=[CH:8][C:7]([O:10][C:11]4[CH:12]=[C:13]([NH:17][C:18]([C:20]5[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=5)=[O:19])[CH:14]=[CH:15][CH:16]=4)=[CH:6][N:5]3[CH:27]=2)=[O:40])[CH2:33][CH2:34]1

Participants

7

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 57749229N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-6-methylpyridine-2-carboxamide

Product 1

HCID 57749386N-[3-({2-[(cyclopropylcarbamoyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-6-methylpyridine-2-carboxamideYield 14%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-6-methylpyridine-2-carboxamide (300 mg, 0.835 mmol) and N,N-diisopropylethylamine (286 μL, 1.67 mmol) in tetrahydrofuran (5 mL) was added 2,2,2-trichloroethylchlorocarbonate (130 μL, 0.944 mmol), and the mixture was stirred at room temperature for 50 min. N,N-Dimethylformamide (5 mL) and cyclopropaneamine (290 μL, 4.19 mmol) were added to the reaction mixture, and the mixture was stirred at 80° C. for 11 hr. The reaction mixture was concentrated under reduced pressure, diluted with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (0%→100% ethyl acetate-hexane) to give the title compound (51.0 mg, 14%) as a white solid.

Workup

  1. stirringthe mixture was stirred at 80° C. for 11 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with aqueous sodium hydrogen carbonate solution
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (0%→100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a19a567d58f34dd0878b5520b66b0266
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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