Trifluoroacetic acid → HCID 67441034, compound

HRID 1400877Notes

Reaction equation

HRID 1400877 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[CH:22]=[N: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[CH:22]=[N: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 67443215HCID 67443215, compound

Product 1

HCID 67441034HCID 67441034, compoundYield 342.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 246 (722 mg, 0.18 mmol) in DCM (30 mL) was added TFA (7 mL) and the reaction mixture was stirred for 45 min. The reaction mixture was concentrated, diluted with water and 4M NaOH to pH 11 and extracted with AcOEt. The extract was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 50 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 15/85 over 20 CV), to produce a material that upon trituration with AcOEt, afforded the title compound 247 (3.15 mg, 0.617 mmol, 52% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 8.71 (s, 1H), 8.44 (d, J=5.6 Hz, 1H), 8.33 (s, 1H), 8.01 (d, J=0.8 Hz, 1H), 7.72 (d, J=2.4 and 13.6 Hz, 1H), 7.68 (s, 1H), 7.35 (t, J=9.2 Hz, 1H), 7.22-7.16 (m, 1H), 6.57 (d, J=2.4 Hz, 1H), 6.53 (d, J=5.6 Hz, 1H), 4.21 (t, J=6.0 Hz, 2H), 3.36 (t, J=5.6 Hz, 2H), 2.98 (s, 3H), 2.97 (t, J=6.0 Hz, 2H), 2.68 (t, J=5.6 Hz, 2H), 2.59-2.50 (m, 1H), 0.68-0.62 (m, 2H), 0.45-0.40 (m, 2H). MS (m/z): 511.54 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water and 4M NaOH to pH 11
  3. extractionextracted with AcOEt
  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 50 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 15/85 over 20 CV)
  9. customto produce a material that upon trituration with AcOEt

Sources & evidence

ORD record
ord-40baa8565627467496ac3c4d7655e8d4
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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