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

HRID 57893
Notes
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Reaction equation

HRID 57893 reaction equation
[CH:1]1([C:4]2[C:5]([N:26]3[CH2:31][CH2:30][CH2:29][C@H:28]([NH:32]C(=O)OC(C)(C)C)[CH2:27]3)=[N:6][C:7]([N:10]3[C:18]4[CH:17]=[C:16]([C:19]5[CH:24]=[N:23][CH:22]=[C:21]([CH3:25])[N:20]=5)[N:15]=[CH:14][C:13]=4[CH:12]=[N:11]3)=[CH:8][CH:9]=2)[CH2:3][CH2:2]1.Cl>CO.O1CCOCC1>[CH:1]1([C:4]2[C:5]([N:26]3[CH2:31][CH2:30][CH2:29][C@H:28]([NH2:32])[CH2:27]3)=[N:6][C:7]([N:10]3[C:18]4[CH:17]=[C:16]([C:19]5[CH:24]=[N:23][CH:22]=[C:21]([CH3:25])[N:20]=5)[N:15]=[CH:14][C:13]=4[CH:12]=[N:11]3)=[CH:8][CH:9]=2)[CH2:2][CH2:3]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86707084tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

Product 1

HCID 86707085(S)-1-(3-cyclopropyl-6-(6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperidin-3-amineYield 49%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent
HCID 31275
1,4-Dioxane
Solvent

Procedure

To a solution of tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (0.2224 mmol; 117.1 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 181 as an off-white solid (46.0 mg, 49%). 1H NMR (400 MHz, DMSO) δ 9.75-9.71 (s, 1H), 9.47-9.44 (s, 1H), 9.33-9.29 (s, 1H), 8.67-8.61 (d, J=9.6 Hz, 2H), 7.55-7.51 (d, J=8.2 Hz, 1H), 7.49-7.43 (d, J=8.2 Hz, 1H), 3.86-3.78 (d, J=10.8 Hz, 1H), 3.65-3.58 (s, 1H), 3.16-3.09 (s, 1H), 2.89-2.81 (m, 1H), 2.68-2.65 (s, 3H), 2.12-2.04 (m, 1H), 2.02-1.93 (d, J=8.9 Hz, 2H), 1.81-1.69 (m, 1H), 1.48-1.37 (d, J=8.7 Hz, 1H), 1.20-1.11 (m, 1H), 1.09-0.99 (m, 1H), 0.91-0.84 (m, 1H), 0.75-0.67 (s, 1H); MS (ESI) m/z: 427.2 [M+H]+

Workup

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

Sources & evidence

ORD record
ord-cee5c7e6dadb4af4845b51c2de848ca1
Source dataset
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09434725B2

Reaction notes

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