Trifluoroacetic acid → HCID 67441967, compound

HRID 1400881Notes

Reaction equation

HRID 1400881 reaction equation
[CH:1]1([NH:4][C:5](=[O:43])[NH:6][C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]=[CH:23][N:24]([CH2:26][CH2:27][N:28]([CH2:36][CH2:37][O:38][CH3:39])C(=O)OC(C)(C)C)[CH:25]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]=[CH:23][N:24]([CH2:26][CH2:27][NH:28][CH2:36][CH2:37][O:38][CH3:39])[CH:25]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)=[O:43])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67441341HCID 67441341, compound

Product 1

HCID 67441967HCID 67441967, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 252 (1 g, 1.63 mmol) in DCM (50 mL) was added TFA (15 mL) and the reaction mixture was stirred for 1.5 h then concentrated, diluted with water and 4M NaOH to pH 11 and extracted with DCM/MeOH. The extract was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 253 (800 mg, 1.56 mmol, 96% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 8.69 (s, 1H), 8.42 (d, J=5.6 Hz, 1H), 7.91 (d, J=1.2 Hz, 1H), 7.75 (d, J=0.8 Hz, 1H), 7.72 (dd, J=2.4 and 13.6 Hz, 1H), 7.66 (s, 1H), 7.36 (t, J=8.8 Hz, 1H), 7.21-7.16 (m, 1H), 6.57 (d, J=2.85 Hz, 1H), 6.54 (d, J=5.6 Hz, 1H), J=6.4 Hz, 2H), 3.36 (t, J=5.6 Hz, 2H), 3.22 (s, 3H), 2.89 (t, J=6.4 Hz, 2H), 2.67 (t, J=5.6. Hz, 2H), 2.58-2.53 (m, 1H), 0.68-0.61 (m, 2H), 0.45-0.40 (m, 2H). MS (m/z): 511.56 (M+H).

Workup

  1. concentrationthen concentrated
  2. additiondiluted with water and 4M NaOH to pH 11
  3. extractionextracted with DCM/MeOH
  4. washThe extract was washed with water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 80 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV)

Sources & evidence

ORD record
ord-17abb3b46f7a43e6b2249bba4cfad942
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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