Dichloromethane → HCID 178519588, compound

HRID 2401774Notes

Reaction equation

HRID 2401774 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:11]=[C:12]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)[S:13][C:14]=2[C:15]2[N:19]=[CH:18][N:17](COCC[Si](C)(C)C)[N:16]=2)[OH:9])=[CH:4][CH:3]=1.C(Cl)Cl.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:11]=[C:12]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)[S:13][C:14]=2[C:15]2[N:19]=[CH:18][NH:17][N:16]=2)[OH:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 68006769HCID 68006769, compound

Product 1

HCID 178519588HCID 178519588, compoundYield 102%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(4-Chlorophenyl)[2-pyridin-4-yl-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-4-yl]methanol (266.0 mg, 0.530 mmol) was dissolved in methylene chloride (3.0 mL, 47 mmol). Trifluoroacetic acid (3.0 mL, 39 mmol) was added and the solution was stirred at rt overnight. After the reaction was completed, saturated NaHCO3 was added and the reaction was stirred at rt for 20 min, then EtOAc (5 mL) was added, the organic layer was separated, washed with brine, dried over MgSO4, filtered, concentrated and the obtained residue was purified by column chromatography (SiO2, elution with 2-20% MeOH in DCM) to give the title compound as a white solid (200 mg). The racemic isomers were separated by chiral prep HPLC to yield 17 (34 mg, 12.7%) (peak 1, ret. time 13.04 min). LCMS: (FA) ES+ , 370. 1H NMR (400 MHz, d6-DMSO) δ: 8.76 (s, 1H), 8.69-8.71 (dd, J=1.5 Hz, 2H), 7.86-7.88 (dd, J=1.5, 2H), 7.55-7.58 (d, J=8.5 Hz, 2H), 7.34-7.38 (d, J=8.5 Hz, 2H), 6.84-6.86 (s, br, 1H) and 70 (34.8 mg, 13.0%) (peak 2, ret. time 13.2 min). LCMS: (FA) ES+ , 370. 1H NMR (400 MHz, d6-DMSO) δ: 8.68-8.72 (m, 3H), 7.86-7.88 (dd, J=1.69 Hz, J=1.5 Hz, 2H), 7.54-7.58 (d, J=8.47 Hz, 2H), 7.34-7.38 (d, J=8.47 Hz, 2H), 6.81-6.82 (s, br, 1H).

Workup

  1. stirringthe reaction was stirred at rt for 20 min
  2. customthe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe obtained residue was purified by column chromatography (SiO2, elution with 2-20% MeOH in DCM)

Sources & evidence

ORD record
ord-bccbaacfc36342228464efb840ae5487
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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