Sodium Hydroxide → N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]cyclopropanecarboxamide

HRID 42257Notes

Reaction equation

HRID 42257 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([NH2:25])[C:13]4[C:17]([CH:18]=3)=[N:16][N:15](C3CCCCO3)[CH:14]=4)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CCN(C(C)C)C(C)C.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1.[OH-].[Na+]>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][NH:16]4)=[C:12]([NH:25][C:38]([CH:35]4[CH2:37][CH2:36]4)=[O:39])[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540492N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]cyclopropanecarboxamideYield 20.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (46 mg, 0.137 mmol) in DCM (1 ml) was added DIPEA (0.119 ml, 0.684 mmol) and cyclopropyl carbonyl chloride (29 mg, 0.274 mmol). The reaction was stirred at room temperature for 1 hour, then 2M sodium hydroxide solution (2 ml) was added and the reaction stirred at room temperature for a further 1 hour. The organic layer was collected by passing through a hydrophobic frit. The aqueous layer was washed several times with DCM. The organic extracts were combined and solvent removed by blow down. The residue was dissolved in methanol (2 ml) and 4M HCl in 1,4-dioxane added (2 ml). The reaction was stirred at room temperature for 1 hour. The solvent was removed by blow down and the residue purified by mass directed preparative HPLC (method B). The residue was freeze dried to give the title compound as a pale brown solid (9 mg).

Workup

  1. stirringthe reaction stirred at room temperature for a further 1 hour
  2. customThe organic layer was collected
  3. washThe aqueous layer was washed several times with DCM
  4. customsolvent removed by blow down
  5. dissolutionThe residue was dissolved in methanol (2 ml)
  6. addition4M HCl in 1,4-dioxane added (2 ml)
  7. stirringThe reaction was stirred at room temperature for 1 hour
  8. customThe solvent was removed by blow down
  9. customthe residue purified by mass
  10. customdried

Sources & evidence

ORD record
ord-5fb2b92beda1432980417bf5d066420a
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Reaction notes

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