Diisopropylethylamine → 8-Trifluoromethoxy-2-oxo-2H-chromene-3-carboxylic acid (2'-trifluoromethoxy-biphenyl-3-yl)-amide

HRID 240090Notes

Reaction equation

HRID 240090 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]([F:28])([F:27])[O:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[C:19]([C:24]([OH:26])=O)=[CH:18]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:53][C:54]([F:70])([F:69])[O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([NH2:68])[CH:63]=1>CN(C=O)C>[F:53][C:54]([F:69])([F:70])[O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([NH:68][C:24]([C:19]2[C:20](=[O:23])[O:21][C:22]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][C:13]=3[O:12][C:11]([F:10])([F:28])[F:27])=[O:26])[CH:63]=1

Participants

6

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 167687363-[2-(Trifluoromethoxy)phenyl]anilineHCID 866503588-Trifluoromethoxy-3-carboxy-coumarin

Product 1

HCID 866503968-Trifluoromethoxy-2-oxo-2H-chromene-3-carboxylic acid (2'-trifluoromethoxy-biphenyl-3-yl)-amideYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIEA (0.011 mL, 0.065 mmol) was added to 8-trifluoromethoxy-3-carboxy-coumarin (0.016 g, 0.059 mmol) and HATU (0.025 g, 0.065 mmol) in 0.36 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 2′-trifluoromethoxy-biphenyl-3-ylamine (0.015 g, 0.059 mmol) was added and allowed to react overnight. DMF was removed under vacuum and the reaction was resuspended in DMSO. The crude product was purified on a Parallex Flex parallel preparative reverse phase HPLC instrument (Biotage) using a solvent gradient of 10-95% ACN/H2O with 0.05% TFA at a flow rate of 20 mL/min. UV absorbance was monitored at 254 nm and the fractions corresponding to the product peak were collected were collected and the solvent removed under vacuum to give 0.027 g of product in 90% yield: LCMS (ESI) m/z 510 (MH+).

Workup

  1. customresulted
  2. customto react overnight
  3. customDMF was removed under vacuum
  4. customThe crude product was purified on a Parallex Flex parallel preparative reverse phase HPLC instrument (Biotage)
  5. customthe fractions corresponding to the product peak were collected
  6. customwere collected
  7. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-b80e82f3a11e4068a1cb3360d5d86f6f
Source dataset
uspto-grants-2014_02
Patent number
US08642788B2

Reaction notes

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