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Hydrochloric Acid → (S)-1-(3-chloro-6-(6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperidin-3-amine

HRID 57887
Notes
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Reaction equation

HRID 57887 reaction equation
[Cl:1][C:2]1[C:3]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30]C(=O)OC(C)(C)C)[CH2:25]2)=[N:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1.Cl>CO.O1CCOCC1>[Cl:1][C:2]1[C:3]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH2:30])[CH2:25]2)=[N:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86707081tert-butyl N-[(3S)-1-[3-chloro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

Product 1

HCID 72715541(S)-1-(3-chloro-6-(6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperidin-3-amineYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent
HCID 31275
1,4-Dioxane
Solvent

Procedure

To a solution of tert-butyl N-[(3S)-1-[3-chloro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (0.140 mmol; 72.7 mg) in Methanol (5 mL) was added hydrochloric acid, 4.0 M in 1,4-Dioxane (5 mL). The resulting mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by reverse phase HPLC to afford 176 as an off-white solid (23.3 mg, 40%). 1H NMR (400 MHz, DMSO) δ 9.67-9.61 (s, 1H), 9.47-9.42 (s, 1H), 9.34-9.28 (s, 1H), 8.71-8.67 (s, 1H), 8.64-8.61 (s, 1H), 8.01-7.94 (d, J=8.4 Hz, 1H), 7.57-7.51 (d, J=8.4 Hz, 1H), 3.91-3.83 (d, J=8.8 Hz, 1H), 3.81-3.72 (d, J=12.3 Hz, 1H), 3.25-3.19 (m, 1H), 2.97-2.89 (m, 1H), 2.77-2.71 (dd, J=11.9, 9.1 Hz, 1H), 2.67-2.62 (d, J=8.6 Hz, 3H), 1.98-1.87 (dd, J=16.2, 6.5 Hz, 2H), 1.84-1.40 (dd, J=32.9, 22.1 Hz, 3H), 1.36-1.23 (td, J=13.5, 4.6 Hz, 1H); MS (ESI) m/z: 421.1 [M+H]+

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d59df29bd81c4f0ca32f6b0539df029f
Source dataset
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09434725B2

Reaction notes

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