Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(3-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 2095949Notes

Reaction equation

HRID 2095949 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[N:11]([CH:13]=[C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])[N:15]=3)[CH:12]=2)=[C:4]([F:24])[CH:3]=1.[F:25][C:26]1[CH:27]=[C:28]([N:32]2[C:37]([CH3:38])=[CH:36][CH:35]=[C:34]([C:39](O)=[O:40])[C:33]2=[O:42])[CH:29]=[CH:30][CH:31]=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.C(=O)([O-])O.[Na+]>CN(C)C=O.O1CCCC1>[CH:19]1([C:17]([NH:16][C:14]2[N:15]=[C:10]3[CH:9]=[CH:8][C:7]([O:6][C:5]4[CH:22]=[CH:23][C:2]([NH:1][C:39]([C:34]5[C:33](=[O:42])[N:32]([C:28]6[CH:29]=[CH:30][CH:31]=[C:26]([F:25])[CH:27]=6)[C:37]([CH3:38])=[CH:36][CH:35]=5)=[O:40])=[CH:3][C:4]=4[F:24])=[CH:12][N:11]3[CH:13]=2)=[O:18])[CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581585401-(3-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158600N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(3-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamideYield 36%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution (5 mL) of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (130 mg, 0.40 mmol), 1-(3-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (120 mg, 0.48 mmol), HATU (180 mg, 0.48 mmol) and N,N-diisopropylethylamine (100 mg, 0.80 mmol) in N,N-dimethylformamide was stirred at room temperature for 5 hr. The reaction solution was divided into two layers with tetrahydrofuran (10 mL) and saturated aqueous sodium hydrogen carbonate solution (10 mL) and the aqueous layer was subjected to extraction (3 times) with ethyl acetate (15 ml). The combined organic layer was washed with water (15 mL) and saturated brine (15 mL), dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the obtained residue was washed with ethyl acetate and collected by filtration to give the title compound (80 mg, 35%) as a brown solid.

Workup

  1. extractionthe aqueous layer was subjected to extraction (3 times) with ethyl acetate (15 ml)
  2. washThe combined organic layer was washed with water (15 mL) and saturated brine (15 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated under reduced pressure
  6. washthe obtained residue was washed with ethyl acetate
  7. filtrationcollected by filtration

Sources & evidence

ORD record
ord-6e39997dc5ca4e0298b3b5b71db07017
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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