Trifluoroacetic acid → HCID 11538025, compound

HRID 416296Notes

Reaction equation

HRID 416296 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C@H:8]2[CH2:12][CH2:11][N:10]([C:13]3[CH:25]=[CH:24][C:16]([C:17]([O:19]C(C)(C)C)=O)=[CH:15][CH:14]=3)[CH2:9]2)[CH:2]=1.FC(F)(F)C(O)=O.CCN(CC)CC.F[P-](F)(F)(F)(F)F.[N:47]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=2[N:49]=N1>C(Cl)Cl.CN(C=O)C>[NH2:47][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=1[NH:49][C:17](=[O:19])[C:16]1[CH:15]=[CH:14][C:13]([N:10]2[CH2:11][CH2:12][C@H:8]([NH:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH2:9]2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 58930436HCID 58930436, compound

Product 1

HCID 11538025HCID 11538025, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of compound 365 (19 mg, 0.56 mmol) in DCM 500 μL was added trifluoroacetic acid (200 μL). The solution was refluxed at 50° C. for 3 h and concentrated in vacuo to produce a white solid. This material was dissolved in DMF (500 μL) and was treated with Et3N (16 μL, 0.118 mmol) and BOP (30 mg, 0.067 mmol). The reaction mixture was stirred for 10 min. and 1,2-henylenediamine (7 mg, 0.061 mmol) and another portion of Et3N (23 μL, 0.168 mmol) were added. The mixture was stirred for 2 h at room temperature and DMF was removed in vacuo at 80° C. The residue was partitioned between EtOAc and H2O. The organic layer was collected and extracted with 1N HCl and neutralized with sat. NaHCO3. A precipitate formed which was extracted with EtOAc, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography using MeOH/CHCl3 (7:93) as the eluent to afford the title compound (11 mg, 52% yield). 1H NMR: (CD3OD) δ(ppm): 7.97 (d, J=2.7 Hz, 1H), 7.86 (d, J=8.8 Hz, 2H), 7.78 (dd, J=4.7, 1.0 Hz, 1H), 7.18-7.10 (m, 3H), 7.05 (td, J=7.4, 0.6 Hz, 1H), 6.89 (dd, J=7.8, 1.2 Hz, 1H), 6.76 (td, J=7.4, 1.4 Hz, 1H), 6.64 (d, J=8.8 Hz, 2H), 4.25 (quint, J=4.9 Hz, 1H), 3.77 (dd, J=10.2, 6.1 Hz, 1H), 3.57 (dd, J=17.0, 7.0 Hz, 1H), 3.49 (td, J=8.0, 5.3 Hz, 1H), 3.29 (q, J=6.7 Hz, 1H), 2.41 (sext, J=7.2 Hz, 1H), 2.10 (sext, J=4.9 Hz, 1H). m/z: 372.4 (MH+).

Workup

  1. concentrationconcentrated in vacuo
  2. customto produce a white solid
  3. stirringThe mixture was stirred for 2 h at room temperature
  4. customDMF was removed in vacuo at 80° C
  5. customThe residue was partitioned between EtOAc and H2O
  6. customThe organic layer was collected
  7. extractionextracted with 1N HCl and neutralized with sat. NaHCO3
  8. customA precipitate formed which
  9. extractionwas extracted with EtOAc
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-2716b25c98934da6901ab48ad276970f
Source dataset
uspto-grants-2012_01
Patent number
US08088805B2

Reaction notes

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