Diisopropylethylamine → 5-Amino-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

HRID 1616037Notes

Reaction equation

HRID 1616037 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.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.[NH:44]1[C:52]2[C:47](=[C:48]([C:53]3[CH:54]=[C:55]([NH2:62])[C:56]4[CH:57]=[N:58][NH:59][C:60]=4[CH:61]=3)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45]1>CN(C=O)C.CS(C)=O.CO.CO>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:62][C:55]2[CH:54]=[C:53]([C:48]3[CH:49]=[CH:50][CH:51]=[C:52]4[C:47]=3[CH:46]=[CH:45][NH:44]4)[CH:61]=[C:60]3[C:56]=2[CH:57]=[N:58][NH:59]3)=[O:10])=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 41797265-Aminopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Product 1

HCID 445398325-Amino-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamideYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a solution of 5-amino-2-pyridinecarboxylic acid (56 mg, 0.40 mmol, available from ChemPacific) in DMF (2 ml) was added HATU (150 mg, 0.40 mmol) and DIPEA (0.211 ml, 1.21 mmol). The mixture was stirred at room temperature for 20 mins then 6-(1H-indol-4-yl)-1H-indazol-4-amine (50 mg, 0.20 mmol) was added and the mixture stirred at room temperature for 18 h. The reaction mixture was added to the top of a 20 g aminopropyl cartridge that had been preconditioned with MeOH. The reaction mixture remained on the cartridges for 3 h before being eluted with MeOH. The solvent was removed in vacuo to give a crude residue that was dissolved in DMSO/MeOH (1:1) and purified by Mass Directed Automated Preparative HPLC (Method C). The product was loaded onto a 1 g aminopropyl column, eluted with DCM/MeOH (1:1) and the solvent removed under a stream of nitrogen to give the title compound (28 mg) as a white solid.

Workup

  1. stirringthe mixture stirred at room temperature for 18 h
  2. additionThe reaction mixture was added to the top of a 20 g aminopropyl cartridge that
  3. waitThe reaction mixture remained on the cartridges for 3 h
  4. washbefore being eluted with MeOH
  5. customThe solvent was removed in vacuo
  6. customto give a crude residue that
  7. custompurified by Mass Directed Automated Preparative HPLC (Method C)
  8. washeluted with DCM/MeOH (1:1)
  9. customthe solvent removed under a stream of nitrogen

Sources & evidence

ORD record
ord-57383f8ef4e04e1bba4899aee3374b40
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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