Benzoic Acid → N-{6-[3-(benzylamino)phenoxy]imidazo[1,2-a]pyridin-2-yl}cyclopropanecarboxamide

HRID 1874558

Reaction equation

HRID 1874558 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[CH:11]=1.[C:24](O)(=O)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.B.O1CCCC1>C(=O)([O-])O.[Na+].O1CCCC1.N1C=CC=CC=1>[CH2:24]([NH:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[CH:11]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 5

HCID 243Benzoic AcidHCID 81531DiisopropylethylamineHCID 2723981Borane;tetrahydrofuranHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57749361N-[6-(3-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57749099N-{6-[3-(benzylamino)phenoxy]imidazo[1,2-a]pyridin-2-yl}cyclopropanecarboxamideYield 30%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-[6-(3-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (20.0 mg, 0.065 mmol), benzoic acid (16.5 mg, 0.135 mmol), HATU (42.3 mg, 0.111 mmol), N,N-diisopropylethylamine (35.0 μL, 0.204 mmol) and pyridine (1.5 mL) was stirred at 60° C. for 4 hr. The reaction solution was concentrated under reduced pressure, and ethyl acetate was added to the residue. The mixture 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, the residue was dissolved in tetrahydrofuran (1.0 mL), and the mixture was stirred at room temperature. A solution (2.0 mL, 2.0 mmol) of 1M borane-tetrahydrofuran-complex/tetrahydrofuran was added thereto, and the mixture was stirred at room temperature for 39 hr. The reaction mixture was diluted with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was concentrated, and the residue was purified by preparative HPLC to give the title compound (7.7 mg, 30%).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, and ethyl acetate
  2. additionwas added to the residue
  3. washThe mixture was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in tetrahydrofuran (1.0 mL)
  8. stirringthe mixture was stirred at room temperature
  9. stirringthe mixture was stirred at room temperature for 39 hr
  10. extractionextracted with ethyl acetate
  11. concentrationThe organic layer was concentrated
  12. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-57d486cf901b43c59f1e38d6f4c52ade
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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