1-Hydroxybenzotriazole → N-{4'-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1'-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide

HRID 859796Notes

Reaction equation

HRID 859796 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:21])[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH:11]=2)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]([OH:30])=O)=[CH:24][CH:23]=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.[NH2:74][CH2:75][CH2:76][CH2:77][N:78]1[CH:82]=[CH:81][N:80]=[CH:79]1>CN(C=O)C>[N:78]1([CH2:77][CH2:76][CH2:75][NH:74][C:28]([C:25]2[CH:24]=[CH:23][C:22]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[C:5]([NH:8][C:9](=[O:21])[C:10]4[CH:15]=[CH:14][N:13]=[C:12]([N:16]5[CH2:17][CH2:18][CH2:19][CH2:20]5)[CH:11]=4)[CH:4]=3)=[CH:27][CH:26]=2)=[O:30])[CH:82]=[CH:81][N:80]=[CH:79]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 787361H-Imidazole-1-propanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 113501482'-Methyl-5'-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 69151799N-{4'-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1'-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamideYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2′-Methyl-5′-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1′-biphenyl-4-carboxylic acid (40 mg, 0.1 mmol), HATU (38 mg, 0.1 mmol), HOBT (13 mg, 0.1 mmol), DIPEA (52 μl), and 1-(3-aminopropyl)imidazole (15 mg, 0.12 mmol) were mixed in DMF (1 ml) and stirred at room temperature for 18 hours. The solvent was evaporated under vacuum and the residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml). The organic phase was applied to a silica gel flash column and eluted with toluene/methanol (8:2), which after evaporation of the solvents under vacuum gave N-{4′-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1′-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide (12 mg, 24%). NMR; δH [2H6]-DMSO 10.31,(1H, s), 8.60,(1H, t), 8.19,(1H, d), 7.93,(2H, d), 7.71,(1H, dd), 7.67,(2H, m), 7.45,(2H, d), 7.30,(1H, d), 7.22,(1H, s), 1.93,(6H, m). LCMS: retention time 2.24 min, MH+509.

Workup

  1. customThe solvent was evaporated under vacuum
  2. customthe residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml)
  3. washeluted with toluene/methanol (8:2), which
  4. customafter evaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-fb62d7ea46b84129bb35144ea1e2703a
Source dataset
uspto-grants-2006_12
Patent number
US07151118B2

Reaction notes

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