1-Hydroxybenzotriazole → N-[6-methyl-4'-({[2-(methylsulphonylamino)ethyl]amino}carbonyl)-1,1'-biphenyl-3-yl]-3-furamide

HRID 2114147Notes

Reaction equation

HRID 2114147 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH3:24])=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([OH:23])=O)=[CH:17][CH:16]=3)[CH:14]=2)=[O:7])=[CH:2]1.[NH2:25][CH2:26][CH2:27][NH:28][S:29]([CH3:32])(=[O:31])=[O:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:24][C:12]1[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([NH:25][CH2:26][CH2:27][NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:23])=[CH:19][CH:20]=2)=[CH:14][C:9]([NH:8][C:6]([C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)=[O:7])=[CH:10][CH:11]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 533845N-(2-Aminoethyl)methanesulfonamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 691521465'-(3-Furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 69200769N-[6-methyl-4'-({[2-(methylsulphonylamino)ethyl]amino}carbonyl)-1,1'-biphenyl-3-yl]-3-furamideYield 90.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (30 mg, 0.093 mmol), N-(2-aminoethyl)methylsulphonamide (12.9 mg, 0.093 mmol), HATU (35.5 mg, 0.093 mmol), HOBT (12.6 mg, 0.093 mmol) and DIPEA (481 μl, 0.28 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum gave N-[6-methyl-4′-({[2-(methylsulphonylamino)ethyl]amino}carbonyl)-1,1′-biphenyl-3-yl]-3-furamide (37 mg, 90%). NMR; δH [2H6]—DMSO 9.91,(1H, s), 8.59,(1H, t), 8.35,(1H, s), 7.92,(2H, d), 7.78,(1H, t), 7.66,(1H, dd), 7.59,(1H, d), 7.45,(2H, d), 7.27,(1H, d), 7.17,(1H, t), 6.98,(1H, m), 3.40,(2H, q), 3.13,(2H, q), 2.91,(3H, s), 2.19,(3H, s). LCMS: retention time 2.82 min, MH+442.

Workup

  1. washwashed with water (2×30ml)
  2. dry with materialdried (magnesium sulphate)
  3. customThe solvent was evaporated under vacuum
  4. customthe residue chromatographed on a silica flash column
  5. washeluting with DCM/methanol/triethylamine (96:2:2)

Sources & evidence

ORD record
ord-257eec32834248939942caf810014bfd
Source dataset
uspto-grants-2008_10
Patent number
US07432289B2

Reaction notes

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