1-(3-Aminopropyl)-4-methylpiperazine → N-(4'-([3-(4-methylpiperazin-1-yl)propylamino]carbonyl)-6-methyl-1,1'-biphenyl-3-yl)-3-furamide

HRID 970223Notes

Reaction equation

HRID 970223 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](O)=[O:22])=[CH:17][CH:16]=3)[CH:14]=2)=[O:7])=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:47][CH2:48][CH2:49][CH2:50][N:51]1[CH2:56][CH2:55][N:54]([CH3:57])[CH2:53][CH2:52]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:57][N:54]1[CH2:55][CH2:56][N:51]([CH2:50][CH2:49][CH2:48][NH:47][C:21]([C:18]2[CH:17]=[CH:16][C:15]([C:13]3[C:12]([CH3:24])=[CH:11][CH:10]=[C:9]([NH:8][C:6]([C:3]4[CH:4]=[CH:5][O:1][CH:2]=4)=[O:7])[CH:14]=3)=[CH:20][CH:19]=2)=[O:22])[CH2:52][CH2:53]1

Participants

6

Reactant 4

HCID 783281-(3-Aminopropyl)-4-methylpiperazineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 691521465'-(3-Furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 69151853N-(4'-([3-(4-methylpiperazin-1-yl)propylamino]carbonyl)-6-methyl-1,1'-biphenyl-3-yl)-3-furamideYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), TBTU (60 mg, 0.186 mmol), 1-(3-aminopropyl)-4-methylpiperazine (25 mg, 0.156 mmol) and DIPEA (81 μl, 0.467 mmol) in DMF (1 ml) were stirred at room temperature for 2 h. The DMF was evaporated under vacuum and the residue dissolved in chloroform and filtered through an aminopropyl SPE (3 g). The filtrate was purified by flash chromatography on silica, eluting with DCM/ethanol/ammonia (110:8:1), which after evaporation of the solvents under vacuum gave N-(4′-{[3-(4-methylpiperazin-1-yl)propylamino]carbonyl)-6-methyl-1,1′-biphenyl-3-yl)-3-furamide (12 mg, 17%). NMR; δH [2H6]-DMSO 9.91,(1H, s), 8.55,(1H, t), 8.35,(1H, s), 7.90,(2H, d), 7.78,(1H, t), 7.66,(1H, dd), 7.59,(1H, d), 7.43,(2H, d), 7.27,(1H, d), 6.98,(1H, m), 3.29,(2H, m), 2.48-2.20,(10H, m), 2.19,(3H, s), 2.13,(3H, s), 1.68,(2H, m). LCMS: retention time 2.37 min, MH+461.

Workup

  1. customThe DMF was evaporated under vacuum
  2. dissolutionthe residue dissolved in chloroform
  3. filtrationfiltered through an aminopropyl SPE (3 g)
  4. customThe filtrate was purified by flash chromatography on silica
  5. washeluting with DCM/ethanol/ammonia (110:8:1), which
  6. customafter evaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-89c3bf37406e4b30913afc663b07bc45
Source dataset
uspto-grants-2007_12
Patent number
US07309800B2

Reaction notes

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