2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 86707149, compound

HRID 57967Notes

Reaction equation

HRID 57967 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][C:26]([OH:29])([CH3:28])[CH2:25][N:24]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[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[CH2:43][C:44]([F:47])([F:46])[F:45])(=O)=O>CN(C=O)C>[OH:29][C:26]1([CH3:28])[CH2:25][N:24]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[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]([CH2:43][C:44]([F:47])([F:46])[F:45])[CH:3]=5)[N:11]=[CH:10][C:9]=4[CH:12]=[N:13]3)[N:20]=2)[CH2:27]1

Participants

4

Reactant 2

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 86707147tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-6-methyl-1,4-diazepane-1-carboxylate

Product 1

HCID 86707149HCID 86707149, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-6-methyl-1,4-diazepane-1-carboxylate (200 mg, 0.41 mmol) in DMF (15 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (473 mg, 2.04 mmol). The reaction mixture was stirred at room temperature for 18 hours, quenched with brine, and extracted with DCM (100 mL×3), and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford tert-butyl(±)-6-hydroxy-6-methyl-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 (183 mg, 78%). MS (ESI) m/z=573 [M+H]+, which was separated by chiral preparative HPLC to afford (R)-tert-butyl 6-hydroxy-6-methyl-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 (51 mg) and (S)-tert-butyl 6-hydroxy-6-methyl-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 (48 mg).

Workup

  1. customquenched with brine
  2. extractionextracted with DCM (100 mL×3)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3595e983149e416d9b954051d070e57b
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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