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

HRID 859797Notes

Reaction equation

HRID 859797 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.[CH3:74][N:75]1[CH2:80][CH2:79][NH:78][CH2:77][CH2:76]1>CN(C=O)C>[CH3:1][C:2]1[C:3]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:78]3[CH2:79][CH2:80][N:75]([CH3:74])[CH2:76][CH2:77]3)=[O:30])=[CH:24][CH:23]=2)=[CH:4][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:6][CH:7]=1

Participants

7

Reactant 5

HCID 531671-MethylpiperazineHCID 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 113501482'-Methyl-5'-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 69151845N-{6-methyl-4'-[(4-methylpiperazin-1-yl)carbonyl]-1,1'-biphenyl-3-yl}2-pyrrolidin-1-ylisonicotinamideYield 29%

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-methylpiperazine (15 mg, 0.12 mmol) were mixed in DMF (1 ml) and stirred at room temperature for 18 h. 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 DCM/ethanol/ammonia (100:8:1 then 40:8:1), which after evaporation of the solvents under vacuum gave N-{6-methyl-4′-[(4-methylpiperazin-1-yl)carbonyl]-1,1′-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide (14 mg, 29%). NMR; δH [2H6]-DMSO 10.26,(1H, s), 8.19,(1H, d), 7.69–7.67,(2H, m), 7.47–7.41,(4H, m), 7.29,(1H, d), 6.96,(1H, d), 6.86,(1H, s), 3.59,(2H, b), 3.43,(4H, m), 2.33,(6H, b), 2.21,(3H, s), 2.21,(3H, s), 1.95,(4H, m). MS: MH+484.

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 DCM/ethanol/ammonia (100:8:1
  4. custom40:8:1), which after evaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-953d201de8bd4cc2a7b63f310498d228
Source dataset
uspto-grants-2006_12
Patent number
US07151118B2

Reaction notes

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