3-Furoic acid → Methyl 5'-(3-furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylate

HRID 970225Notes

Reaction equation

HRID 970225 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][C:58]1[CH:59]=[CH:60][C:61]([CH3:74])=[C:62]([C:64]2[CH:69]=[CH:68][C:67]([C:70]([O:72][CH3:73])=[O:71])=[CH:66][CH:65]=2)[CH:63]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:1]1[CH:5]=[CH:4][C:3]([C:6]([NH:57][C:58]2[CH:59]=[CH:60][C:61]([CH3:74])=[C:62]([C:64]3[CH:69]=[CH:68][C:67]([C:70]([O:72][CH3:73])=[O:71])=[CH:66][CH:65]=3)[CH:63]=2)=[O:8])=[CH:2]1

Participants

7

Reactant 5

HCID 102683-Furoic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21090583Methyl 5'-amino-2'-methyl-1,1'-biphenyl-4-carboxylate

Product 1

HCID 69152621Methyl 5'-(3-furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Furoic acid (557 mg, 4.97 mmol), HATU (1.89 g, 4.97 mmol), HBTU (560 mg, 4.14 mmol), methyl 5′-amino-2′-methyl-1,1′-biphenyl-4-carboxylate (1.0 g, 4.14 mmol) and DIPEA (2.17 ml, 12.43 mmol) were mixed in DMF (5 ml) and the reaction stirred at room temperature for 18 h. The DMF was evaporated under vacuum, the residue partitioned between DCM (50 ml) and aqueous sodium carbonate (1M, 50 ml) and the aqueous extracted with DCM (2×30 ml). The combined organics were washed with brine (75 ml), dried (magnesium sulphate) and concentrated under vacuum. The residue was purified on a silica flash column eluting with DCM/ethanol/ammonia (500:8:1), which after evaporation of the solvents under vacuum gave methyl 5′-(3-furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylate (800 mg, 58%). LCMS: retention time 3.41 min, MH+336.

Workup

  1. customThe DMF was evaporated under vacuum
  2. customthe residue partitioned between DCM (50 ml) and aqueous sodium carbonate (1M, 50 ml)
  3. extractionthe aqueous extracted with DCM (2×30 ml)
  4. washThe combined organics were washed with brine (75 ml)
  5. dry with materialdried (magnesium sulphate)
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified on a silica flash column
  8. washeluting with DCM/ethanol/ammonia (500:8:1), which
  9. customafter evaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-e6aa9c41d08246a39ec251fa1b1e7f13
Source dataset
uspto-grants-2007_12
Patent number
US07309800B2

Reaction notes

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