1,4-Dioxane → (3S)-1-[6-[6-(6-ethylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperidin-3-amine

HRID 57858Notes

Reaction equation

HRID 57858 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N:20]3[C:28]4[CH:27]=[C:26]([C:29]5[CH:34]=[N:33][CH:32]=[C:31]([CH2:35][CH3:36])[N:30]=5)[N:25]=[CH:24][C:23]=4[CH:22]=[N:21]3)[N:15]=2)[CH2:9]1)(C)(C)C.O1CCOCC1>Cl>[CH2:35]([C:31]1[N:30]=[C:29]([C:26]2[N:25]=[CH:24][C:23]3[CH:22]=[N:21][N:20]([C:16]4[N:15]=[C:14]([N:10]5[CH2:11][CH2:12][CH2:13][C@H:8]([NH2:7])[CH2:9]5)[CH:19]=[CH:18][CH:17]=4)[C:28]=3[CH:27]=2)[CH:34]=[N:33][CH:32]=1)[CH3:36]

Participants

4

Reactant 2

HCID 312751,4-Dioxane2×HCID 86707056(S)-tert-butyl (1-(6-(6-(6-ethylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperidin-3-yl)carbamate

Product 1

HCID 89914637(3S)-1-[6-[6-(6-ethylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperidin-3-amineYield 73.3%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of (5)-tert-butyl(1-(6-(6-(6-ethylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperidin-3-yl)carbamate (80 mg, 0.16 mmol) in hydrogen chloride (4 mol/l) in 1,4-dioxane (2.0 ml, 8.0 mmol) and 1,4-dioxane 2.0 mL was stirred at RT 18 h. The reaction was concentrated and submitted for reverse phase HPLC to give 156 (47 mg) in 50% yield. 1H NMR (400 MHz, DMSO) δ 9.55 (s, 1H), 9.49 (s, 1H), 9.33 (s, 1H), 8.66 (d, J=4.9 Hz, 2H), 7.75 (t, J=8.1 Hz, 1H), 7.21 (d, J=7.7 Hz, 1H), 6.82 (d, J=8.5 Hz, 1H), 4.42 (d, J=13.1 Hz, 1H), 4.12 (d, J=10.6 Hz, 1H), 3.17-3.06 (m, 1H), 2.93 (q, J=7.5 Hz, 2H), 2.88-2.71 (m, 2H), 1.84 (ddd, J=17.0, 13.4, 8.1 Hz, 2H), 1.58 (dd, J=24.7, 11.5 Hz, 1H), 1.35 (t, J=7.6 Hz, 3H). MS (ESI) m/z: 401.2.

Workup

  1. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-1ecd813fc2fa432f96157b8204294baf
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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