Carbonate Ion → Trifluoroacetic acid

HRID 521249Notes

Reaction equation

HRID 521249 reaction equation
[C:1](ON1C(=O)CCC1=O)(ON1C(=O)CCC1=O)=[O:2].[F:19][CH:20]([F:23])[CH2:21][OH:22].[C:24]([CH2:26][C:27]1([N:34]2[CH:38]=[C:37]([C:39]([NH2:41])=[O:40])[C:36]([NH:42][C:43]3[CH:48]=[CH:47][N:46]=[C:45]([F:49])[CH:44]=3)=[N:35]2)[CH2:32][CH2:31][NH:30][CH2:29][CH:28]1[F:33])#[N:25].[C:50](=[O:53])([O-])[O-:51]>CC#N.CS(C)=O>[C:50]([OH:51])([C:20]([F:23])([F:33])[F:19])=[O:53].[C:39]([C:37]1[C:36]([NH:42][C:43]2[CH:48]=[CH:47][N:46]=[C:45]([F:49])[CH:44]=2)=[N:35][N:34]([C:27]2([CH2:26][C:24]#[N:25])[CH2:32][CH2:31][N:30]([C:1]([O:22][CH2:21][CH:20]([F:23])[F:19])=[O:2])[CH2:29][CH:28]2[F:33])[CH:38]=1)(=[O:40])[NH2:41]

Participants

8

Reactant 4

HCID 19660Carbonate IonHCID 1361872,2-Difluoroethan-1-olHCID 676246Di(succinimido) carbonateHCID 86729429HCID 86729429, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 86729428HCID 86729428, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 1,1′-[carbonylbis(oxy)]dipyrrolidine-2,5-dione (51 mg, 0.20 mmol) in MeCN (0.5 mL) were added TEA (0.093 mL, 0.66 mmol) and 2,2-difluoroethanol (16 mg, 0.20 mmol). The resulting mixture was stirred for 2 hours at ambient temperature. 1-(4-(Cyanomethyl)-3-fluoropiperidin-4-yl)-3-((2-fluoropyridin-4-yl)amino)-1H-pyrazole-4-carboxamide (60 mg, 0.17 mmol) dissolved in DMSO (0.3 mL) and MeCN (0.5 mL) was added to the mixed carbonate solution and heated to 65° C. for 16 hours. The mixture was filtered and purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier) to afford the title compound. LRMS (ESI) calc'd for C19H19F4N7O3 [M+H]+: 470. Found: 470.

Workup

  1. temperatureheated to 65° C. for 16 hours
  2. filtrationThe mixture was filtered
  3. custompurified by reverse-phase preparative HPLC (MeCN/water

Sources & evidence

ORD record
ord-6e0e67049e5d4053bde48f37aaabd0a6
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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