Trifluoroacetic acid → (S)-1-(5-((2-aminopropanamido)methyl)thiophen-2-yl)-N-benzyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

HRID 2196515Notes

Reaction equation

HRID 2196515 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[N:15]([C:16]2[S:20][C:19]([CH2:21][NH:22][C:23](=[O:34])[C@@H:24]([NH:26]C(=O)OC(C)(C)C)[CH3:25])=[CH:18][CH:17]=2)[N:14]=[C:13]([C:35]([F:38])([F:37])[F:36])[CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:26][C@@H:24]([CH3:25])[C:23]([NH:22][CH2:21][C:19]1[S:20][C:16]([N:15]2[C:11]([C:9]([NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])=[CH:12][C:13]([C:35]([F:36])([F:38])[F:37])=[N:14]2)=[CH:17][CH:18]=1)=[O:34]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69095062(S)-tert-butyl 1-((5-(5-(benzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 25218479(S)-1-(5-((2-aminopropanamido)methyl)thiophen-2-yl)-N-benzyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamideYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 26a (24 mg, 0.044 mmol) in CH2Cl2 (0.44 mL) was added trifluoroacetic acid (44 μL, 0.571 mmol). The mixture was stirred for 2 h at room temperature. The solvent was then evaporated and the residue was purified by silica gel column chromatography with gradient of MeOH (5-20%) in CH2Cl2. The residue was purified by prep-HPLC using an Aquasil C18 column with gradient of MeOH (5-95%) in water to afford 27a (7.7 mg, 39%) as a white solid. 1H NMR (DMSO-d6) δ(ppm): 9.41 (t, J=5.7 Hz, 1H), 8.69 (m, 1H), 8.28 (s, 1H), 7.41 (s, 1H), 7.33 (d, J=6.8 Hz, 2H), 7.28-7.24 (m, 3H), 7.05 (d, J=3.3 Hz, 1H), 6.86 (d, J=3.9 Hz, 1H), 4.44 (m, 2H), 4.40 (d, J=5.9 Hz, 2H), 3.44 (q, J=6.8 Hz, 1H), 1.20 (d, J=6.8 Hz, 3H). LRMS: calc 451.1; found 452.5 (MH)+.

Workup

  1. customThe solvent was then evaporated
  2. customthe residue was purified by silica gel column chromatography with gradient of MeOH (5-20%) in CH2Cl2
  3. customThe residue was purified

Sources & evidence

ORD record
ord-4dd804e9dd59404dac85ae2f2ed8023f
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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