Ammonia → N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1H-benzimidazole-2-carboxamide

HRID 42245

Reaction equation

HRID 42245 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([OH:12])=O.[NH:13]1[C:21]2[C:16](=[C:17]([C:22]3[CH:23]=[C:24]([NH2:37])[C:25]4[C:29]([CH:30]=3)=[N:28][N:27](C3CCCCO3)[CH:26]=4)[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1.CCN(C(C)C)C(C)C.N>CN(C=O)C.CO>[NH:13]1[C:21]2[C:16](=[C:17]([C:22]3[CH:30]=[C:29]4[C:25]([CH:26]=[N:27][NH:28]4)=[C:24]([NH:37][C:10]([C:2]4[NH:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)=[O:12])[CH:23]=3)[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2332402-Benzimidazolecarboxylic acidHCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540221N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1H-benzimidazole-2-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

1H-Benzimidazole-2-carboxylic acid (available from Apollo Scientific, 25 mg, 0.151 mmol), O-(7-Azabenzatriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (63 mg, 0.17 mmol) and 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (50 mg, 0.15 mmol) were dissolved in anhydrous DMF (3 ml) and then treated with DIPEA (0.05 ml, 0.30 mmol). The reactions were then stirred at room temperature for 15 hours. The mixture was treated with methanol (3 ml) and then Macroporous-Tosic Acid (170 mg, 0.75 mmol) then stirred for 15 hours. The mixture was then treated with 0.88 ammonia solution (0.60 ml), stirred for 10 minutes, then filtered and solvent blown off under a stream of nitrogen. The crude residue was purified by Mass Directed Automated Preparative HPLC (Method B) to give after evaporation of solvents the title compound as a yellow solid (27 mg). LCMS (Method B) m/z 393 [MH+], Rt=1.04 min.

Workup

  1. stirringstirred for 10 minutes
  2. filtrationfiltered
  3. customThe crude residue was purified by Mass Directed Automated Preparative HPLC (Method B)
  4. customto give
  5. customafter evaporation of solvents the title compound as a yellow solid (27 mg)

Sources & evidence

ORD record
ord-faf48123d94743ae808c61a29cfd745c
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Linked notes

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