Diisopropylethylamine → (3-Fluoroazetidin-1-yl)(8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

HRID 931050Notes

Reaction equation

HRID 931050 reaction equation
[O:1]1[C:5]([C:6]2[C:7]3[N:8]([C:16]([C:19](O)=[O:20])=[CH:17][N:18]=3)[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)=[CH:4][N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:47][CH:48]1[CH2:51][NH:50][CH2:49]1.C(N(CC)C(C)C)(C)C>O.CN(C=O)C>[F:47][CH:48]1[CH2:51][N:50]([C:19]([C:16]2[N:8]3[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=[C:6]([C:5]4[O:1][CH:2]=[N:3][CH:4]=4)[C:7]3=[N:18][CH:17]=2)=[O:20])[CH2:49]1

Participants

7

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 101250543-fluoroazetidine HydrochlorideHCID 1183789628-(1,3-Oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 118378942(3-Fluoroazetidin-1-yl)(8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanoneYield 92.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (100 mg), HATU (154 mg), 3-fluoroazetidine hydrochloride (45.0 mg), N,N-diisopropylethylamine (0.147 mL) and DMF (2 mL) was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and recrystallized from ethyl acetate/hexane to give the title compound (110 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
  6. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-e4b69ff4a1f34a8c9a3e792ddece4de3
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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