Trifluoroacetic acid → 3-[(1-{3-Cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile

HRID 575508Notes

Reaction equation

HRID 575508 reaction equation
[C:1]([CH2:3][CH:4]([N:23]1[CH:27]=[C:26]([C:28]2[C:29]3[CH:36]=[CH:35][N:34](COCC[Si](C)(C)C)[C:30]=3[N:31]=[CH:32][N:33]=2)[CH:25]=[N:24]1)[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[C:19]([F:21])[CH:20]=2)[C:16]#[N:17])[CH:8]([F:22])[CH2:7]1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH2:3][CH:4]([N:23]1[CH:27]=[C:26]([C:28]2[C:29]3[CH:36]=[CH:35][NH:34][C:30]=3[N:31]=[CH:32][N:33]=2)[CH:25]=[N:24]1)[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[C:19]([F:21])[CH:20]=2)[C:16]#[N:17])[CH:8]([F:22])[CH2:7]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 696750943-[(1-{3-Cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile

Product 1

HCID 696749183-[(1-{3-Cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrileYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[(1-{3-cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile (11 mg, 0.018 mmol) in DCM (0.5 mL) was added 0.5 ml TFA. The mixture was stirred for 1 hour and solvent was removed. The residue was dissolved in methanol (1 mL), and 0.2 ml EDA was added. After stirring for 2 hours, The reaction solution was diluted with methanol and purified by preparative-LCMS (C18 column eluting with a gradient of ACN/H2O containing 0.15% NH4OH) afforded product (5.4 mg, 62%). The product was synthesized from diastereomer 1 using same procedure in 61% yield LCMS (M+H)+: 489.2.

Workup

  1. customsolvent was removed
  2. dissolutionThe residue was dissolved in methanol (1 mL)
  3. addition0.2 ml EDA was added
  4. stirringAfter stirring for 2 hours
  5. additionThe reaction solution was diluted with methanol
  6. custompurified by preparative-LCMS (C18 column
  7. washeluting with a gradient of ACN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-daadef1911f643ca87c3bb6c954d67ca
Source dataset
uspto-grants-2015_05
Patent number
US09034884B2

Reaction notes

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