Water → Trifluoroacetic acid

HRID 1522590Notes

Reaction equation

HRID 1522590 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([F:36])=[C:13]([C:15]2[CH:20]=[C:19]([NH:21][C:22]3[C:23]4[C:24](=[CH:28][N:29]([CH2:31][C@H:32]([OH:35])[CH2:33][OH:34])[N:30]=4)[N:25]=[CH:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)[CH:14]=1.C1COCC1.O.C(O)(C(F)(F)F)=O>CS(C)=O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([F:36])=[C:13]([C:15]2[CH:20]=[C:19]([NH:21][C:22]3[C:23]4[C:24](=[CH:28][N:29]([CH2:31][C@H:32]([OH:35])[CH2:33][OH:34])[N:30]=4)[N:25]=[CH:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)[CH:14]=1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 86704366HCID 86704366, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 54670125HCID 54670125, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(S)-3-(7-(2-(5-Chloro-2-fluorophenyl)pyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)propane-1,2-diol TFA salt was dissolved in 600 ml a 1:1 mix of THF and water then added 5 μL of TFA and the reaction mixture was stirred for 2 hours at room temperature before being concentrated to give a residue. The residue was dissolved in DMSO and purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 10-25% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give the title compound as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.38-3.55 (2H, m) 3.98-4.08 (1H, m) 4.39-4.52 (2H, m) 4.66-4.76 (2H, m) 7.26 (1H, d, J=6.57 Hz) 7.46 (1H, dd, J=10.74, 8.72 Hz) 7.57-7.66 (2H, m) 7.96-8.00 (1H, m) 8.02 (1H, dd, J=6.57, 2.78 Hz) 8.49-8.58 (1H, m) 8.72 (1H, s) 8.73-8.82 (1H, m) 11.34 (1H, s). MS [M+H] found 414.3.

Workup

  1. concentrationbefore being concentrated
  2. customto give a residue
  3. custompurified by preparative HPLC
  4. washeluting with a gradient of 10-25% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-3ee956d0e1a24e86aeffe47d2eccdf96
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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