Acetic Acid → HCID 178465801, compound

HRID 1714452Notes

Reaction equation

HRID 1714452 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][O:17]C1CCCCO1)[C:9](=O)[CH2:8][CH2:7]2)[CH3:2].[F:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=S)[CH:29]=[CH:30][CH:31]=1.C[Si](C)(C)[Si](C)(C)C.[Li].[NH2:44][NH2:45].C(O)(=O)C>C(OCC)(=O)C.C1COCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][OH:17])[C:9]1=[N:44][NH:45][C:33]([NH:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([F:25])[CH:27]=3)=[C:8]1[CH2:7]2)[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 98343-Fluorophenyl isothiocyanate2×HCID 18445696HCID 18445696, compoundHCID 57425481Lithium hexamethyldisilane

Product 1

HCID 178465801HCID 178465801, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-Ethoxy-6-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-indan-1-one, (Intermediate Z) (0.100 g, 0.0003 mol), 3-fluorophenyl isothiocyanate (Compound 4a) (0.043 mL, 0.00036 mol) and THF (3 mL) was added lithium hexamethyldisilane (0.360 mL, 0.00036 mol) dropwise at room temperature with stirring. The reaction mixture was stirred for 5 h. Hydrazine (0.011 mL, 0.00036 mol) and acetic acid (0.021 mL, 0.00036 mol) was added to the reaction mixture, which was then heated at reflux temperature for 12 h. The reaction solution was then diluted with ethyl acetate, washed with water and dried over MgSO4. The solvent was removed in vacuo and the crude material was purified on the reverse phase HPLC and converted to the desired product upon standing in the 0.1% TFA solution. Lyophilization yielded the title compound as a white powder. MS m/z 384.4 (M+H)+;

Workup

  1. stirringThe reaction mixture was stirred for 5 h
  2. temperaturewas then heated
  3. temperatureat reflux temperature for 12 h
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customthe crude material was purified on the reverse phase HPLC

Sources & evidence

ORD record
ord-648d87e400614e7b95c427e497434191
Source dataset
uspto-grants-2010_09
Patent number
US07795440B2

Reaction notes

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