Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]-N'-phenylcyclopropane-1,1-dicarboxamide

HRID 2095899Notes

Reaction equation

HRID 2095899 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[N:12]=[C:11]3[S:13][C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])=[N:15][C:10]3=[CH:9][CH:8]=2)=[C:4]([F:24])[CH:3]=1.[C:25]1([NH:31][C:32]([C:34]2([C:37](O)=[O:38])[CH2:36][CH2:35]2)=[O:33])[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.C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[CH:19]1([C:17]([NH:16][C:14]2[S:13][C:11]3[C:10]([N:15]=2)=[CH:9][CH:8]=[C:7]([O:6][C:5]2[CH:22]=[CH:23][C:2]([NH:1][C:37]([C:34]4([C:32]([NH:31][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[O:33])[CH2:36][CH2:35]4)=[O:38])=[CH:3][C:4]=2[F:24])[N:12]=3)=[O:18])[CH2:21][CH2:20]1

Participants

7

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 190968711-(Phenylcarbamoyl)cyclopropanecarboxylic acidHCID 58158529N-[5-(4-amino-2-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158514N-[4-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-3-fluorophenyl]-N'-phenylcyclopropane-1,1-dicarboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-[5-(4-amino-2-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.436 mmol) in N,N-dimethylacetamide (3.0 mL) were added 1-(phenylcarbamoyl)cyclopropanecarboxylic acid (134 mg, 0.653 mmol), HATU (248 mg, 0.653 mmol) and N,N-diisopropylethylamine (114 μL, 0.653 mmol), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate alone). The obtained powder was washed with hexane/ethyl acetate and collected by filtration to give the title compound (175 mg, 76%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate alone)
  7. washThe obtained powder was washed with hexane/ethyl acetate
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-234515f44c114cdc86150cc6115a3fd2
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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