Diisopropylethylamine → 4-(4'-Methoxy-biphenyl-4-ylcarbamoyl) 5-methyl-furan-2-carboxylic acid

HRID 1786572Notes

Reaction equation

HRID 1786572 reaction equation
C[O:2][C:3]([C:5]1[O:6][C:7]([CH3:13])=[C:8]([C:10]([OH:12])=O)[CH:9]=1)=[O:4].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:47][O:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[CH:59][C:58]([NH2:61])=[CH:57][CH:56]=2)=[CH:51][CH:50]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:47][O:48][C:49]1[CH:50]=[CH:51][C:52]([C:55]2[CH:60]=[CH:59][C:58]([NH:61][C:10]([C:8]3[CH:9]=[C:5]([C:3]([OH:2])=[O:4])[O:6][C:7]=3[CH3:13])=[O:12])=[CH:57][CH:56]=2)=[CH:53][CH:54]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27595644-Amino-4'-methoxybiphenylHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 184446775-(Methoxycarbonyl)-2-methylfuran-3-carboxylic acid

Product 1

HCID 184445754-(4'-Methoxy-biphenyl-4-ylcarbamoyl) 5-methyl-furan-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-methyl-furan-2,4-dicarboxylic acid-2-methyl ester (23) (100 mg) in N,N-dimethylformamide (3.0 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (228 mg), diisopropylethylamine (0.56 mL) and 4′-methoxy-biphenyl-4-ylamine (120 mg). The resulting solution was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate (20 mL) and washed successively with water (2×20 mL), 0.1 M hydrochloric acid (20 mL), water (20 mL), saturated sodium hydrogen carbonate (10 mL) and brine (10 mL). This solution was dried and concentrated in vacuo. The residue (170 mg) was dissolved in dichloromethane (5 mL), treated with triethylamine (0.3 mL) and a scavenger resin PS-TsCl (0.6 g) and the mixture shaken for 3 hours at room temperature. The reaction mixture was filtered and concentrated in-vacuo. The residue was dissolved in methanol/tetrahydrofuran (1:3 by volume) (20 mL), treated with 1.0 M aqueous lithium hydroxide solution (2.0 mL) and allowed to stir at room temperature for 4 hours. The pH of the reaction mixture was adjusted to between pH 4 and pH 5 by careful addition of 1.0 M hydrochloric acid (1.0 mL) and partly concentrated in vacuo.

Workup

  1. washwashed successively with water (2×20 mL), 0.1 M hydrochloric acid (20 mL), water (20 mL), saturated sodium hydrogen carbonate (10 mL) and brine (10 mL)
  2. customThis solution was dried
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue (170 mg) was dissolved in dichloromethane (5 mL)
  5. additiontreated with triethylamine (0.3 mL)
  6. stirringa scavenger resin PS-TsCl (0.6 g) and the mixture shaken for 3 hours at room temperature
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated in-vacuo
  9. dissolutionThe residue was dissolved in methanol/tetrahydrofuran (1:3 by volume) (20 mL)
  10. additiontreated with 1.0 M aqueous lithium hydroxide solution (2.0 mL)
  11. stirringto stir at room temperature for 4 hours
  12. additionThe pH of the reaction mixture was adjusted to between pH 4 and pH 5 by careful addition of 1.0 M hydrochloric acid (1.0 mL)
  13. concentrationpartly concentrated in vacuo

Sources & evidence

ORD record
ord-05d5003fdcd942298997f09dcba031a1
Source dataset
uspto-grants-2009_03
Patent number
US07507754B2

Reaction notes

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