2,2,2-Trifluoroethanol → 2,2,2-Trifluoroethyl 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

HRID 521236Notes

Reaction equation

HRID 521236 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)[C:9](=[O:10])C1.FC(F)(F)C([O-])=O.[C:32]([C:35]1[C:36]([NH:49][C:50]2[CH:55]=[CH:54][N:53]=[C:52]([F:56])[CH:51]=2)=[N:37][N:38]([C:40]2([CH2:46][C:47]#[N:48])[CH2:45][CH2:44][NH2+:43][CH2:42][CH2:41]2)[CH:39]=1)(=[O:34])[NH2:33]>C(#N)C.CS(C)=O>[C:32]([C:35]1[C:36]([NH:49][C:50]2[CH:55]=[CH:54][N:53]=[C:52]([F:56])[CH:51]=2)=[N:37][N:38]([C:40]2([CH2:46][C:47]#[N:48])[CH2:41][CH2:42][N:43]([C:9]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[O:10])[CH2:44][CH2:45]2)[CH:39]=1)(=[O:34])[NH2:33]

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 676246Di(succinimido) carbonateHCID 867293964-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate

Product 1

HCID 867294102,2,2-Trifluoroethyl 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2,2,2-trifluoroethanol (15 mg, 0.15 mmol) in acetonitrile (1.0 mL) was added TEA (0.043 mL, 0.31 mmol) followed by N,N′-disuccinimidyl carbonate (59 mg, 0.23 mmol). The resulting mixture was allowed to stir at ambient temperature for 4 hours. A solution of 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-4) (70 mg, 0.15 mmol) and TEA (0.043 mL, 0.31 mmol) in DMSO (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The crude reaction mixture was cooled to ambient temperature and purified directly by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound, Example #30-1.

Workup

  1. temperatureThe resulting mixture was heated to 50° C.
  2. stirringto stir for 16 hours
  3. customThe crude reaction mixture
  4. temperaturewas cooled to ambient temperature
  5. custompurified directly by reverse-phase preparative HPLC (MeCN/water
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fa420e99ee4941bd938942298c08621e
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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