Trifluoroacetic acid → HCID 67460621, compound

HRID 1400814Notes

Reaction equation

HRID 1400814 reaction equation
[CH:1]1([NH:4][C:5](=[O:45])[NH:6][C:7]2[CH:43]=[CH:42][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][C:29]6=[O:41])=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:44])[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:43]=[CH:42][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]=[CH:23][C:24]([CH2:27][N:28]6[CH2:33][CH2:32][NH:31][CH2:30][C:29]6=[O:41])=[CH:25][N:26]=5)[S:20][C:13]=34)=[C:9]([F:44])[CH:8]=2)=[O:45])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67442974HCID 67442974, compound

Product 1

HCID 67460621HCID 67460621, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 71 (60 mg, 0.095 mmol) and TFA (5 mL) in DCM (20 mL) was stirred at RT for 5 h. The TFA was removed by co-evaporation with DCM and MeOH, diluted with water, and the pH was adjusted to around 12 with 1N NaOH. The resultant gel was extracted with DCM with traces of MeOH. The combined organic extract was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 10 g column; 2% of ammonium hydroxide in MeOH/DCM; 0/100 to 10/90 over 20 CV, 10/90 to 20/80 over 10 CV then 20/80 over 5 CV), to afford the title compound 72 (35 mg, 0.066 mmol, 69% yield, traces of TFA) as a white sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.72 (s, 1H), 8.55 (d, J=1.8 Hz, 1H), 8.52 (d, J=5.3 Hz, 1H), 8.35 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.83 (dd, J=8.2, 2.2 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (dd, J=8.9, 1.5 Hz, 1H), 6.65 (dd, J=5.3, 0.6 Hz, 1H), 6.58 (bd, J=2.7 Hz, 1H), 4.59 (s, 2H), 3.37 (s, 2H), 3.28 (t, J=5.5 Hz, 2H), 2.95 (t, J=5.4 Hz, 2H), 2.59-2.51 (m, 1H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H), one NH is missing. MS (m/z): 533.4 (M+H).

Workup

  1. customThe TFA was removed by co-evaporation with DCM and MeOH
  2. additiondiluted with water
  3. extractionThe resultant gel was extracted with DCM with traces of MeOH
  4. extractionThe combined organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 10 g column

Sources & evidence

ORD record
ord-56c4f6d0a3dc4dbebb365c39d1111be6
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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