Potassium Carbonate → tert-butyl(+/-)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

HRID 57900Notes

Reaction equation

HRID 57900 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[N:11]=[CH:10][C:9]3[CH:12]=[N:13][N:14]([C:15]4[N:20]=[C:19]([N:21]5[CH2:27][CH:26]([OH:28])[CH2:25][N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:23][CH2:22]5)[CH:18]=[CH:17][CH:16]=4)[C:8]=3[CH:7]=2)[CH:3]=[N:2]1.FC(F)(F)S(O[CH2:42][C:43]([F:46])([F:45])[F:44])(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[OH:28][CH:26]1[CH2:25][N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:23][CH2:22][N:21]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([N:14]3[C:8]4[CH:7]=[C:6]([C:4]5[CH:5]=[N:1][N:2]([CH2:42][C:43]([F:46])([F:45])[F:44])[CH:3]=5)[N:11]=[CH:10][C:9]=4[CH:12]=[N:13]3)[N:20]=2)[CH2:27]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 86707091tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate

Product 1

HCID 86707092tert-butyl(+/-)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylateYield 46.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate (150 mg, 0.32 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (110 mg, 0.48 mmol), and K2CO3 (87 mg, 0.64 mmol) in DMF (10 mL) was stirred at room temperature for 18 hours, which was monitored by LCMS. After completion of the reaction, the reaction mixture was quenched with EtOAc (100 mL), washed with brine (50 mL), dried over MgSO4, concentrated under reduced pressure. The residue was purified by silica gel chromatography using petroleum ether/EtOAc (1/1) as eluting solvents to afford tert-butyl(±)-6-hydroxy-4-(6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate as a white solid (82 mg, 46.5%). MS (ESI) m/z: 559 [M+H]+.

Workup

  1. customAfter completion of the reaction
  2. customthe reaction mixture was quenched with EtOAc (100 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washas eluting solvents

Sources & evidence

ORD record
ord-e3955e4f243840f1b190e715861d6978
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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