Trifluoroacetic acid → HCID 44229703, compound

HRID 1026830Notes

Reaction equation

HRID 1026830 reaction equation
[F:1][C:2]1[CH:36]=[C:35]([NH:37][C:38](=[O:50])[CH2:39][C:40]([NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[F:49])=[O:41])[CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]([CH3:32])[C:16]([CH2:19][N:20]([CH2:28][CH2:29][O:30][CH3:31])C(=O)OC(C)(C)C)=[CH:17][N:18]=3)[S:13][C:6]=12.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:36]=[C:35]([NH:37][C:38](=[O:50])[CH2:39][C:40]([NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[F:49])=[O:41])[CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]([CH3:32])[C:16]([CH2:19][NH:20][CH2:28][CH2:29][O:30][CH3:31])=[CH:17][N:18]=3)[S:13][C:6]=12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58236655HCID 58236655, compound

Product 1

HCID 44229703HCID 44229703, compoundYield 40.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 354 (230 mg, 0.325 mmol) in DCM (3 mL) was added TFA (0.5 mL). The reaction mixture was stirred at room temperature overnight then concentrated. The residue was partitioned between EtOAc and NaHCO3 saturated solution. The organic layer was collected, dried and concentrated. The residue was purified via Biotage (0-50% MeOH/EA; 10 g SNAP column) to afford a reddish solid which was purified again by flash column chromatography (eluent MeOH/EA, 20-25%) to give a yellowish solid which was triturated with ether to afford the title compound 355 (80 mg, 0.132 mmol, 40.5% yield) as an off-white solid. HNMR (dmso) d (ppm) 1H: 10.53 (s, 1H), 10.01 (s, 1H), 8.47 (d, 1H, J=5.5 Hz), 7.95 (m, 1H), 7.85-7.81 (m, 2H), 7.46 (t, 1H, J=8.8 Hz), 7.39 (d, 1H, J=10.9 Hz), 7.15-7.09 (m, 2H), 6.91 (s, 1H), 6.65 (d, 1H, J=5.5 Hz), 3.81 (s, 3H), 3.72 (s, 2H), 3.58 (s, 2H), 3.35 (t, 2H, J=5.6 Hz), 3.20 (s, 3H), 2.64 (t, 2H, J=5.6 Hz). MS: 607.2 (MH)+.

Workup

  1. concentrationthen concentrated
  2. customThe residue was partitioned between EtOAc and NaHCO3 saturated solution
  3. customThe organic layer was collected
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified via Biotage (0-50% MeOH/EA; 10 g SNAP column)
  7. customto afford a reddish solid which
  8. customwas purified again by flash column chromatography (eluent MeOH/EA, 20-25%)
  9. customto give a yellowish solid which
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-7693e540880a4e43972c603ed6377c11
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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