Trifluoroacetic acid → HCID 178474034, compound

HRID 2402079Notes

Reaction equation

HRID 2402079 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:37]2[CH2:40][CH:39]([N:41]([CH3:43])[CH3:42])[CH2:38]2)[C:9]2[CH:10]=[C:11]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=3)[S:12][C:13]=2[C:14]2[N:18]=[CH:17][N:16](COCC[Si](C)(C)C)[N:15]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([N:37]2[CH2:38][CH:39]([N:41]([CH3:42])[CH3:43])[CH2:40]2)[C:9]2[CH:10]=[C:11]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=3)[S:12][C:13]=2[C:14]2[NH:18][CH:17]=[N:16][N:15]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68006840HCID 68006840, compound

Product 1

HCID 178474034HCID 178474034, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{4-[4-{(4-chlorophenyl)[3-(dimethylamino)azetidin-1-yl]methyl}-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridin-2-yl}acetamide (60 mg, 0.094 mmol) was dissolved in dichloromethane (1.19 mL) and trifluoroacetic acid (0.30 mL, 3.85 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo and distributed between EtOAc and saturated NaHCO3 solution. The aqueous layer was extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (SiO2, elution with methanol in dichloromethane, 0-20% gradient) to afford the title compound as a white solid (34.2 mg, 71.6%). LCMS: (AA) ES+ 508, 510; 1H NMR (400 MHz, d4-methanol): 8.51 (s, 1H), 8.39 (s, 1H), 8.24 (br s, 1H), 7.78 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.32 (br s, 1H), 7.26 (d, J=8.4 Hz, 2H), 5.71 (s, 1H), 3.45-3.36 (m, 2H), 3.00-2.83 (m, 3H), 2.19 (s, 3H), 2.06 (s, 6H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. extractionThe aqueous layer was extracted with EtOAc twice
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (SiO2, elution with methanol in dichloromethane, 0-20% gradient)

Sources & evidence

ORD record
ord-444165162dc147f98b8c1e4cfa377423
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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