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

HRID 1529274Notes

Reaction equation

[CH3:1][CH:2]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16](C2CCCCO2)[N:15]=[C:14]3[C:26]2[N:31]=[C:30]([O:32][C@@H:33]3[CH2:38][CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34]3)[CH:29]=[N:28][CH:27]=2)[CH:8]=[N:7][CH:6]=1)[CH3:3].Cl>CO>[CH3:3][CH:2]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[C:26]2[CH:27]=[N:28][CH:29]=[C:30]([O:32][C@@H:33]3[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]3)[N:31]=2)[CH:8]=[N:7][CH:6]=1)[CH3:1]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of tert-butyl (3R)-3-((6-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate (0.130 g, 0.21 mmol) in MeOH (2.0 mL) was added HCl (5 M in IPA, 4.2 mL, 21.11 mmol, Acros). The mixture was heated at 80° C. for 30 min. The crude reaction was cooled to RT and concentrated to a yellow 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-(6-(1-methylethoxy)-2-pyrazinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indazole as a pink solid. MS (ESI, pos. ion) m/z: 432.2 (M+1).

Workup

customThe crude reaction
temperaturewas cooled to RT
concentrationconcentrated to a yellow solid
additionthat was slurried with a 1/1 mixture of DCM/MeOH (2 mL)
washa pre-washed (5 mL MeOH) of Si-propylsulfonic acid (Silicycle, Cat# R51230B)
washThe column was washed with MeOH (10 mL)

Sources & evidence

ORD record: ord-3a85206bcd1a4785bf7be9da073f39a8
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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