1-Hydroxybenzotriazole → N-(6-Methyl-4'-{[3-(4-methylpiperazin-1-yl)anilino]carbonyl}-1,1'-biphenyl-3-yl)-3-furamide

HRID 859804Notes

Reaction equation

HRID 859804 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.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:33]=[C:34]([CH:36]=[CH:37][CH:38]=2)[NH2:35])[CH2:28][CH2:27]1.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:35][C:34]3[CH:36]=[CH:37][CH:38]=[C:32]([N:29]4[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]4)[CH:33]=3)=[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 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 115646133-(4-Methylpiperazin-1-yl)anilineHCID 691521465'-(3-Furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 69152871N-(6-Methyl-4'-{[3-(4-methylpiperazin-1-yl)anilino]carbonyl}-1,1'-biphenyl-3-yl)-3-furamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 3-(4-methylpiperazin-1-yl)aniline (29.8 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 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 (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanoltriethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{([3-(4-methylpiperazin-1-yl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (59.5 mg, 77%). NMR; δH [2H6]-DMSO 10.13,(1H, s), 9.93,(1H, s), 8.36,(1H, s), 8.02,(2H, d), 7.78,(1H, t), 7.68,(1H, dd), 7.63,(1H, d), 7.51,(2H, d), 7.43,(1H, m), 7.30–7.26,(2H, m), 7.17,(1H, t), 6.99,(1H, m), 6.70,(1H, dd), 3.12,(4H, m), 2.46,(4H, m), 2.22,(6H, s). LCMS: retention time 2.43 min, MH+495.

Workup

  1. washwashed with water (2×30 ml)
  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/methanoltriethylamine (96:2:2)

Sources & evidence

ORD record
ord-530e87e7ed0440bd95fdec6f86725bba
Source dataset
uspto-grants-2006_12
Patent number
US07151118B2

Reaction notes

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