Diisopropylethylamine → HCID 58158494, compound

HRID 2095913Notes

Reaction equation

HRID 2095913 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([F:10])([F:9])[F:8])=[C:5]([C:11](O)=[O:12])[C:4](=[O:14])[N:3]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[NH2:21][C:22]1[CH:43]=[CH:42][C:25]([O:26][C:27]2[CH:28]=[CH:29][C:30]3[N:31]([CH:33]=[C:34]([NH:36][C:37]([CH:39]4[CH2:41][CH2:40]4)=[O:38])[N:35]=3)[CH:32]=2)=[C:24]([F:44])[CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.O1CCCC1.CN(C)C=O>[CH:39]1([C:37]([NH:36][C:34]2[N:35]=[C:30]3[CH:29]=[CH:28][C:27]([O:26][C:25]4[CH:42]=[CH:43][C:22]([NH:21][C:11]([C:5]5[C:4](=[O:14])[N:3]([C:15]6[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=6)[N:2]([CH3:1])[C:6]=5[C:7]([F:10])([F:9])[F:8])=[O:12])=[CH:23][C:24]=4[F:44])=[CH:32][N:31]3[CH:33]=2)=[O:38])[CH2:40][CH2:41]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 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideHCID 66968907HCID 66968907, compound

Product 1

HCID 58158494HCID 58158494, compoundYield 48.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

A mixture of 1-methyl-3-oxo-2-phenyl-5-(trifluoromethyl)-2,3-dihydro-1H-pyrazole-4-carboxylic acid (450 mg, 1.6 mmol), N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (360 mg, 1.1 mmol), HATU (590 mg, 1.6 mmol), diisopropylethylamine (430 mg, 3.3 mmol) and N,N-dimethylformamide (7 mL) was stirred at room temperature for 13 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution were added to the mixture, and the aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=40/60→100/0) to give the title compound (320 mg, 48%) as a pale-yellow solid.

Workup

  1. extractionthe aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran
  2. washThe combined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=40/60→100/0)

Sources & evidence

ORD record
ord-11431465ac1d4575a1ab97d362934a2f
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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