Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-N'-(4-fluoro-2-methylphenyl)cyclopropane-1,1-dicarboxamide

HRID 2095902Notes

Reaction equation

HRID 2095902 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:31]=[CH:30][C:29]([NH:32][C:33]([C:35]2([C:38](O)=[O:39])[CH2:37][CH2:36]2)=[O:34])=[C:28]([CH3:41])[CH:27]=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>CN(C)C=O.C(OCC)(=O)C.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:38]([C:35]5([C:33]([NH:32][C:29]6[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=6[CH3:41])=[O:34])[CH2:37][CH2:36]5)=[O:39])=[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 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581584691-[(4-Fluoro-2-methylphenyl)carbamoyl]cyclopropanecarboxylic acidHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158580N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-N'-(4-fluoro-2-methylphenyl)cyclopropane-1,1-dicarboxamideYield 45%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-[6-(4-Amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.46 mmol), 1-[(4-fluoro-2-methylphenyl)carbamoyl]cyclopropanecarboxylic acid (120 mg, 0.51 mmol) and HATU (230 mg, 0.60 mmol) were suspended in N,N-dimethylformamide (3.0 mL), and N,N-diisopropylethylamine (0.16 mL, 0.92 mmol) was added. After stirring at room temperature for 8 hr, the reaction mixture was diluted with ethyl acetate (5.0 mL) and tetrahydrofuran (5.0 mL). The mixture was washed twice with saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, ethyl acetate was added to the residue, and the resulting precipitate was collected by filtration. The obtained precipitate was recrystallized from ethanol/water to give the title compound (110 mg, 45%) as a white solid.

Workup

  1. washThe mixture was washed twice with saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. customThe solvent was evaporated under reduced pressure, ethyl acetate
  4. additionwas added to the residue
  5. filtrationthe resulting precipitate was collected by filtration
  6. customThe obtained precipitate was recrystallized from ethanol/water

Sources & evidence

ORD record
ord-3379939d457249f7a21c7930e63834ee
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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