Trifluoroacetic acid → methyl 2-({[1-(5-{[(2S)-2-aminopropanamido]methyl}thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]formamido}methyl)benzoate

HRID 2196505Notes

Reaction equation

HRID 2196505 reaction equation
C(OC([NH:8][C@@H:9]([CH3:42])[C:10]([NH:12][CH2:13][C:14]1[S:18][CH:17]=[C:16]([N:19]2[C:23]([C:24]([NH:26][CH2:27][C:28]3[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=3[C:30]([O:32][CH3:33])=[O:31])=[O:25])=[CH:22][C:21]([C:38]([F:41])([F:40])[F:39])=[N:20]2)[CH:15]=1)=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C@@H:9]([CH3:42])[C:10]([NH:12][CH2:13][C:14]1[S:18][CH:17]=[C:16]([N:19]2[C:23]([C:24]([NH:26][CH2:27][C:28]3[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=3[C:30]([O:32][CH3:33])=[O:31])=[O:25])=[CH:22][C:21]([C:38]([F:39])([F:41])[F:40])=[N:20]2)[CH:15]=1)=[O:11]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69300597(S)-methyl 2-((1-(5-((2-(tert-butoxycarbonylamino)propanamido)methyl)thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamido)methyl)benzoate

Product 1

HCID 25218477methyl 2-({[1-(5-{[(2S)-2-aminopropanamido]methyl}thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]formamido}methyl)benzoateYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Compound 15f (108 mg, 0.177 mmol) was shaken in a solution of DCM (0.7 mL) and TFA (0.3 mL) for 1 hour. The reaction was then diluted with DCM and concentrated under reduced pressure. More DCM was added to the residue and then removed again by reduced pressure. The residue was then dissolved in ethyl acetate and washed with saturated NaHCO3 (3×). The aqueous phases were combined and extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over Na2SO4, filtered and concentrated to give the compound 9 h (89.3 mg, 99% yield) as a white crust. 1H NMR (CD3OD) δ(ppm): 7.97 (d, J=8.0 Hz, 1H), 7.56 (t, J=7.2 Hz, 1H), 7.46-7.44 (m, 2H), 7.41 (t, J=7.6 Hz, 1H), 7.12 (s, 1H), 7.09 (s, 1H), 4.82 (s, 2H), 4.51 (d, J=15.6 Hz, 1H), 4.98 (d, J=15.6 Hz, 1H), 3.89 (s, 3H), 3.42 (q, 1H), 1.27 (d, J=6.8 Hz, 3H). LRMS (ESI): calc 509.1; found 510.1 (MH)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionMore DCM was added to the residue
  3. customremoved again by reduced pressure
  4. dissolutionThe residue was then dissolved in ethyl acetate
  5. washwashed with saturated NaHCO3 (3×)
  6. extractionextracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the compound 9 h (89.3 mg, 99% yield) as a white crust

Sources & evidence

ORD record
ord-c3ab2144bccc4e19958d785d1169b5ed
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

Loading…