Cesium carbonate → 1-(6-(6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-6-ol

HRID 57920Notes

Reaction equation

HRID 57920 reaction equation
F[C:2]1[N:7]=[C:6]([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:5]=[CH:4][C:3]=1[C:24]([F:27])([F:26])[F:25].Br.Br.[NH:30]1[CH2:36][CH:35]([OH:37])[CH2:34][NH:33][CH2:32][CH2:31]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.CC(O)C>[CH3:23][C:19]1[N:18]=[C:17]([C:14]2[N:13]=[CH:12][C:11]3[CH:10]=[N:9][N:8]([C:6]4[N:7]=[C:2]([N:30]5[CH2:36][CH:35]([OH:37])[CH2:34][NH:33][CH2:32][CH2:31]5)[C:3]([C:24]([F:27])([F:25])[F:26])=[CH:4][CH:5]=4)[C:16]=3[CH:15]=2)[CH:22]=[N:21][CH:20]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 426145691,4-Diazepan-6-ol dihydrobromideHCID 867071101-[6-Fluoro-5-(trifluoromethyl)-2-pyridyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine

Product 1

HCID 727144771-(6-(6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-6-olYield 11%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-[6-fluoro-5-(trifluoromethyl)-2-pyridyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine (0.213 mmol; 79.9 mg), 1,4-diazepan-6-ol dihydrobromide (1.07 mmol; 297 mg), and cesium carbonate (2.13 mmol; 696 mg) in DMSO (2 mL) and IPA (4 mL) in a sealed pressure vial was heated at 120° C. overnight. The mixture was cooled to room temperature, and then filtered through Celite®. The filtrate was concentrated and the residue was purified by reverse phase HPLC to afford 219 as an off-white solid (10.8 mg, 11%). 1H NMR (400 MHz, DMSO) δ 9.59-9.53 (s, 1H), 9.48-9.43 (s, 1H), 9.38-9.33 (s, 1H), 8.79-8.75 (s, 1H), 8.66-8.62 (s, 1H), 8.22-8.17 (d, J=8.5 Hz, 1H), 7.57-7.52 (d, J=8.5 Hz, 1H), 4.76-4.67 (s, 1H), 3.98-3.88 (d, J=10.4 Hz, 3H), 3.75-3.66 (d, J=14.1 Hz, 1H), 3.65-3.55 (dd, J=15.3, 8.4 Hz, 1H), 3.15-3.07 (m, 1H), 3.06-2.99 (m, 1H), 2.87-2.79 (dd, J=13.7, 3.4 Hz, 1H), 2.76-2.68 (dd, J=13.6, 5.8 Hz, 1H), 2.69-2.62 (s, 3H); MS (ESI) m/z: 471.1 [M+H]+

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered through Celite®
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7863b57b9eef4657b35ff86c7e914a24
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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