Hydrochloric Acid → HCID 86638191, compound

HRID 2355301Notes

Reaction equation

HRID 2355301 reaction equation
[ClH:1].OC1C(C(F)(F)F)=C(OCC2C=CC=C(CNC)C=2)C=CC=1C(=O)C.CN1C(C(O)=O)=CN=C1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[C:66]([C:69]1[CH:93]=[CH:92][C:72]([O:73][CH2:74][C:75]2[CH:76]=[C:77]([CH:89]=[CH:90][CH:91]=2)[CH2:78][N:79]([CH3:88])[C:80]([C:82]2[N:83]([CH3:87])[CH:84]=[N:85][CH:86]=2)=[O:81])=[C:71]([C:94]([F:97])([F:96])[F:95])[C:70]=1[OH:98])(=[O:68])[CH3:67].Cl>O1CCCC1.C(OCC)(=O)C.CO>[ClH:1].[C:66]([C:69]1[CH:93]=[CH:92][C:72]([O:73][CH2:74][C:75]2[CH:76]=[C:77]([CH:89]=[CH:90][CH:91]=2)[CH2:78][N:79]([CH3:88])[C:80]([C:82]2[N:83]([CH3:87])[CH:84]=[N:85][CH:86]=2)=[O:81])=[C:71]([C:94]([F:95])([F:96])[F:97])[C:70]=1[OH:98])(=[O:68])[CH3:67]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27735071-methyl-1H-imidazole-5-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 59153163HCID 59153163, compoundHCID 68454016HCID 68454016, compound

Product 1

HCID 86638191HCID 86638191, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Stir 1-[2-hydroxy-4-(3-methylaminomethyl-benzyloxy)-3-trifluoromethyl-phenyl]-ethanone hydrochloride (200 mg, 0.51 mmol), 3-methyl-3H-imidazole-4-carboxylic acid (96 mg, 0.76 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (173 mg, 0.9 mmol), 1-hydroxybenzotriazole monohydrate (123 mg, 0.9 mmol) and triethylamine (350 uL, 2.5 mmol) in tetrahydrofuran (15 mL). After 16 hrs, dilute the reaction mixture with ethyl acetate and wash with aqueous sodium carbonate solution. Dry the organic portion over sodium sulfate. Filter and concentrate. Chromatograph the crude material on silica gel eluting with 4% methanol/dichloromethane to provide the coupling product: the 3-methyl-3H-imidazole-4-carboxylic acid [3-(4-acetyl-3-hydroxy-2-trifluoromethyl-phenoxymethyl)-benzyl]-methyl-amide. Dissolve it in methanol, add 5N hydrogen chloride. Concentrate to a minimal volume. Add ethyl acetate to precipitate a white solid. Collect the solid, wash it with ethyl acetate and vacuum-dry to provide the title compound (186 mg). MS (m/z): 462.2 (M+1, free base).

Workup

  1. washwash with aqueous sodium carbonate solution
  2. dry with materialDry the organic portion over sodium sulfate
  3. filtrationFilter
  4. concentrationconcentrate
  5. customChromatograph the crude material on silica gel eluting with 4% methanol/dichloromethane to provide the coupling product
  6. concentrationConcentrate to a minimal volume
  7. customAdd ethyl acetate to precipitate a white solid
  8. customCollect the solid
  9. washwash it with ethyl acetate
  10. customvacuum-dry

Sources & evidence

ORD record
ord-fd8fbcd1e4ed4913aea94b49057af5cd
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

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