Hydrochloric Acid → 5-(5-methoxy-3-pyridinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indazole

HRID 1529270Notes

Reaction equation

HRID 1529270 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14](C2CCCCO2)[N:13]=[C:12]3[C:24]2[N:29]=[C:28]([O:30][C@@H:31]3[CH2:36][CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32]3)[CH:27]=[N:26][CH:25]=2)[CH:6]=[N:7][CH:8]=1.Cl>CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[C:12]3[C:24]2[CH:25]=[N:26][CH:27]=[C:28]([O:30][C@@H:31]3[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]3)[N:29]=2)[CH:6]=[N:7][CH:8]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86709759tert-butyl (3R)-3-((6-(5-(5-methoxy-3-pyridinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate

Product 1

HCID 679597765-(5-methoxy-3-pyridinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indazole

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (3R)-3-((6-(5-(5-methoxy-3-pyridinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate (0.062 g, 0.106 mmol) and HCl (5 M in i-PrOH, 2.114 mL, 10.57 mmol, Acros) in 1 ml of MeOH and 1 mL of DCM was heated at reflux for 30 min. The crude reaction was cooled to RT and concentrated to a yellowish-green solid that was slurried with a 1/1 mixture of DCM/MeOH (2 mL) and applied to a pre-washed (5 mL MeOH) of Si-propylsulfonic acid (Silicycle, Cat# R51230B). The column was washed with MeOH (10 mL). The compound was released with 15 mL of 2 M NH3 in MeOH to afford 5-(5-methoxy-3-pyridinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indazole as an off-white foam. MS (ESI, pos. ion) m/z: 403.1 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 min
  3. customThe crude reaction
  4. concentrationconcentrated to a yellowish-green solid that
  5. additionwas slurried with a 1/1 mixture of DCM/MeOH (2 mL)
  6. washa pre-washed (5 mL MeOH) of Si-propylsulfonic acid (Silicycle, Cat# R51230B)
  7. washThe column was washed with MeOH (10 mL)

Sources & evidence

ORD record
ord-2a970ae405654e81a5c488cc005cf75a
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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