1-Hydroxybenzotriazole → HCID 10187199, compound

HRID 970216Notes

Reaction equation

HRID 970216 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.[CH3:31][N:32](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=[N:61][C:59]=2C=1.[CH3:65][CH2:66][N:67]([CH:71]([CH3:73])C)[CH:68]([CH3:70])C>CN(C=O)C>[CH3:1][C:2]1[C:3]([C:22]2[CH:23]=[CH:24][C:25]([C:28]([NH:32][CH2:31][CH2:73][CH2:71][N:67]3[CH2:66][CH2:65][N:61]([CH3:59])[CH2:70][CH2:68]3)=[O:30])=[CH:26][CH:27]=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

6

Reactant 4

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

Product 1

HCID 10187199HCID 10187199, compoundYield 89%

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-aminomethyl)-4-methylpiperazine (19 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 toluene/methanol (8:2, 7:3, 6:4), which after evaporation of the solvents under vacuum gave N-(6-methyl-4′-{[3-(4-methylpiperazin-1-yl)propylamino]carbonyl}-1,1′-biphenyl-3-yl)-2-pyrrolidin-1-ylisonicotinamide (48 mg, 89%). NMR; δH [2H6]-DMSO 10.51,(1H, s), 8.68,(1H, t), 8.17,(1H, d), 7.93,(2H, d), 7.76,(1H, dd), 7.72,(1H, d), 7.42,(2H, d), 7.28,(1H, d), 7.00,(1H, d), 6.95,(1H, d), 3.43,(4H, m), 3.29,(2H, q), 2.49-2.32,(10H, m), 2.21-2.19,(6H, m), 1.94,(4H, m), 1.70,(2H, m). LCMS: retention time 2.13 min, MH+541.

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, 7:3, 6:4), which
  4. customafter evaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-ab6b5cfb67a34ef8badb35015f785177
Source dataset
uspto-grants-2007_12
Patent number
US07309800B2

Reaction notes

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