Trifluoroacetic acid → HCID 67442611, compound

HRID 1400808Notes

Reaction equation

HRID 1400808 reaction equation
[CH:1]1([NH:4][C:5](=[O:42])[NH:6][C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]4[CH:20]=[C:21]([C:23]5[N:28]=[CH:27][C:26]([CH2:29][N:30]([CH2:38][CH2:39][O:40][CH3:41])C(=O)OC(C)(C)C)=[CH:25][CH:24]=5)[S:22][C:15]=34)=[CH:9][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:8]=[CH:9][C:10]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]4[CH:20]=[C:21]([C:23]5[CH:24]=[CH:25][C:26]([CH2:29][NH:30][CH2:38][CH2:39][O:40][CH3:41])=[CH:27][N:28]=5)[S:22][C:15]=34)=[CH:11][N:12]=2)=[O:42])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67441888HCID 67441888, compound

Product 1

HCID 67442611HCID 67442611, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 28 (754 mg, 1.27 mmol) and TFA (5 mL) in DCM (25 mL) was stirred at RT for 5.5 hr. The TFA was removed by co-evaporation with DCM, dissolved in a minimum of methanol, diluted with water, and the pH was adjusted to around 13 with 1N NaOH. The resulting sticky suspension was extracted with DCM in the presence of traces of methanol. The combined organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by Biotage (SiliaSep 40 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 10/90 over 20 CV) to produce a material that upon trituration with MeOH afforded the title compound 29 (360 mg, 0.734 mmol, 67% yield over 2 steps) as a white fluffy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.23 (bs, 1H), 8.56 (d, J=1.6 Hz, 1H), 8.51 (d, J=5.5 Hz, 1H), 8.31 (s, 1H), 8.27-8.20 (m, 2H), 7.89 (dd, J=8.2, 2.2 Hz, 1H), 7.79-7.72 (m, 2H), 7.66 (bd, J=9.0 Hz, 1H), 6.69 (d, J=5.5 Hz, 1H), 3.78 (s, 2H), 3.41 (t, J=5.9 Hz, 2H), 3.24 (s, 3H), 2.68-2.57 (m, 3H), 0.74-0.60 (m, 2H), 0.52-0.39 (m, 2H), one NH is missing. MS (m/z): 491.6 (M±H).

Workup

  1. customThe TFA was removed by co-evaporation with DCM
  2. dissolutiondissolved in a minimum of methanol
  3. additiondiluted with water
  4. extractionThe resulting sticky suspension was extracted with DCM in the presence of traces of methanol
  5. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SiliaSep 40 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 10/90 over 20 CV)
  9. customto produce a material that upon trituration with MeOH

Sources & evidence

ORD record
ord-76f4ea76c85d45d1ad5f0df0c1ca2de5
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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