Diisopropylethylamine → 2-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid [2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amide

HRID 470337Notes

Reaction equation

HRID 470337 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C:16]1[NH:17][C:18]2[CH:24]=[C:23]([C:25](O)=[O:26])[CH:22]=[CH:21][C:19]=2[N:20]=1.Cl.Cl.[CH3:30][O:31][C:32]1[CH:37]=[C:36]([N:38]2[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]2)[CH:35]=[CH:34][C:33]=1[NH2:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:30][O:31][C:32]1[CH:37]=[C:36]([N:38]2[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]2)[CH:35]=[CH:34][C:33]=1[NH:45][C:25]([C:23]1[CH:22]=[CH:21][C:19]2[N:20]=[C:16]([C:3]3[CH:4]=[C:5]([C:8]4[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=4)[CH:6]=[CH:7][C:2]=3[OH:1])[NH:17][C:18]=2[CH:24]=1)=[O:26]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686686372-Methoxy-4-(4-methylpiperazin-1-yl)aniline dihydrochlorideHCID 1361063252-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid

Product 1

HCID 1361062932-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid [2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amideYield 46.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[2-hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid (containing 1 equivalent of DMA, 44 mg, 0.1 mmol), 2-methoxy-4-(4-methyl-piperazin-1-yl)-phenylamine di HCl salt (29.4 mg, 0.1 mmol) and HATU (38 mg, 0.1 mmol) in DMF (1.2 mL) was added DIEA (45 mg, 0.35 mmol). The reaction mixture was stirred at room temperature for 2 h and heated at 60° C. for 3 h, and then evaporated to dry under reduced pressure. The residue was diluted with DMSO (1.5 mL), filtered and then purified with using HPLC (TFA/H2O/CH3CN) to afford the title compound (26.4 mg, 39%). ESI-MS m/z 565.5 (MH+).

Workup

  1. temperatureheated at 60° C. for 3 h
  2. customevaporated
  3. customto dry under reduced pressure
  4. additionThe residue was diluted with DMSO (1.5 mL)
  5. filtrationfiltered
  6. custompurified with using HPLC (TFA/H2O/CH3CN)

Sources & evidence

ORD record
ord-68274bde35af4c279bb3817290ff1252
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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