Trifluoroacetic acid → HCID 68738719, compound

HRID 1752574Notes

Reaction equation

HRID 1752574 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18](C(OC(C)(C)C)=O)[N:17]=[C:16]3[NH:29][C:30](=[O:33])[CH2:31]Br)[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:34]([N:37]([CH:40]([CH3:42])C)CC)([CH3:36])C.N1CCCC1.FC(F)(F)C(O)=O>C(#N)C>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][N:17]=[C:16]3[NH:29][C:30](=[O:33])[CH2:31][N:37]2[CH2:34][CH2:36][CH2:42][CH2:40]2)[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 68738058HCID 68738058, compound

Product 1

HCID 68738719HCID 68738719, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Example 305A (44 mg, 0.086 mmol) and diisopropylethylamine (0.015 mL, 0.086 mmol) in acetonitrile (1 mL) was added pyrrolidine (0.021 mL, 0.25 mmol) and the reaction mixture was heated at about 60° C. for about 15 minutes. The reaction mixture was cooled to ambient temperature and trifluoroacetic acid (1 mL) was added. The reaction mixture was heated at about 60° C. for about 48 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane (20 mL) and washed with 15% aqueous sodium hydroxide solution (20 mL). The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by reverse-phase HPLC using acetonitrile/water (0.05 M ammonium acetate) gradient elution method to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1H), 8.24 (s, 1H), 7.81 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.27-7.45 (m, 5H), 5.64 (s, 2H), 3.35 (s, 2H), 2.65 (s, 4H), 1.76 (s, 4H). MS (ESI+) m/z 402 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. temperatureThe reaction mixture was heated at about 60° C. for about 48 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with dichloromethane (20 mL)
  5. washwashed with 15% aqueous sodium hydroxide solution (20 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by reverse-phase
  11. washacetonitrile/water (0.05 M ammonium acetate) gradient elution method

Sources & evidence

ORD record
ord-1ef9db3b1e55480387dc1d9573efc2c8
Source dataset
uspto-grants-2015_10
Patent number
US09163007B2

Reaction notes

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