Hydrochloric Acid → 1-(5-(5-(2,6-difluorophenyl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-amine

HRID 1529351Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](C1CCCCO1)[N:13]=[C:12]2[C:24]1[CH:25]=[C:26]([N:30]2[CH2:35][CH2:34][CH:33]([NH:36]C(=O)OC(C)(C)C)[CH2:32][CH2:31]2)[CH:27]=[N:28][CH:29]=1.Cl>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:24]1[CH:25]=[C:26]([N:30]2[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]2)[CH:27]=[N:28][CH:29]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (120 mg, 0.204 mmol) in dioxane (5 mL) was treated with concentrated HCl (0.113 mL, 2.035 mmol). The reaction was heated to 85° C. After 1 h, the reaction was cooled to 23° C. and concentrated. The residue (as HCl salt) was free-based using a Silicycle Si-propylsulfonic acid ion exchange column (catalog # R51230B). The compound was diluted in MeOH and added to a pad of the resin (wetted and flushed with 10 mL MeOH). It was flushed with MeOH (50 mL), and then the product was “released” using 2.0 M NH3 in MeOH solution (50 ml). The final filtrate was concentrated, affording 1-(5-(5-(2,6-difluorophenyl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-amine. MS (ESI, pos. ion) m/z: 406.2 (M+1).

Workup

temperaturethe reaction was cooled to 23° C.
concentrationconcentrated
additionThe compound was diluted in MeOH
additionadded to a pad of the resin (wetted and flushed with 10 mL MeOH)
customIt was flushed with MeOH (50 mL)
concentrationThe final filtrate was concentrated

Sources & evidence

ORD record: ord-2b51d7bcd5db4d02b276bf4bfb3a1f71
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

Loading…