Tetrahydrofuran → HCID 66817781, compound

HRID 1755023Notes

Reaction equation

HRID 1755023 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.[I-].C[S+](C)(C)=O.C(OC(=O)[N:28](C1C=C(C)C(/C=C/S(N2CCC3(N=C(C4CCC(C)CC4)NC3=O)CC2)(=O)=O)=C(C)C=1)C)(C)(C)C.[Cl-].[NH4+].C([O:68][C:69](=O)[N:70]([C:72]1[CH:77]=[C:76]([CH3:78])[C:75]([CH:79]2[CH2:81][CH:80]2[S:82]([N:85]2[CH2:102][CH2:101][C:88]3([N:92]=[C:91]([CH:93]4[CH2:98][CH2:97][CH:96]([CH3:99])[CH2:95][CH2:94]4)[NH:90][C:89]3=[O:100])[CH2:87][CH2:86]2)(=[O:84])=[O:83])=[C:74]([CH3:103])[CH:73]=1)[CH3:71])(C)(C)C>CN1CCN(C)C1=O.C(OCC)(=O)C>[CH3:78][C:76]1[CH:77]=[C:72]([N:70]([CH3:71])[C:69]([NH2:28])=[O:68])[CH:73]=[C:74]([CH3:103])[C:75]=1[C:79]([CH3:81])=[CH:80][S:82]([N:85]1[CH2:102][CH2:101][C:88]2([N:92]=[C:91]([CH:93]3[CH2:94][CH2:95][CH:96]([CH3:99])[CH2:97][CH2:98]3)[NH:90][C:89]2=[O:100])[CH2:87][CH2:86]1)(=[O:83])=[O:84]

Participants

9

Reactant 6

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 2724254Sodium bis(trimethylsilyl)amideHCID 66818374HCID 66818374, compoundHCID 70895755HCID 70895755, compound

Product 1

HCID 66817781HCID 66817781, compound

Reagents, catalysts & solvents 2

HCID 66611,3-Dimethyl-2-imidazolidinoneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (0.31 mL, 0.306 mmol) was added to a mixture of trimethylsulfoxonium iodide (29 mg, 0.131 mmol) in 1,3-dimethyl-2-imidazolidinone (2 mL) at room temperature. The reaction solution was stirred at room temperature for 0.5 hour. A mixed solution of (3,5-dimethyl-4-{(E)-2-[2-(4-methyl-cyclohexyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-vinyl}-phenyl)-methyl-carbamic acid tert-butyl ester (50 mg, 0.0873 mmol) in 1,3-dimethyl-2-imidazolidinone (2 mL) was then added at room temperature, and the mixture was heated with stirring at 50° C. for 15 hours. After returning to room temperature, an aqueous ammonium chloride solution and ethyl acetate were added to the reaction solution. The organic layer and the aqueous layer were separated, and the aqueous layer was repeatedly extracted with ethyl acetate three times. The organic layers were combined, washed with water twice and saturated brine, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give a mixture of (3,5-dimethyl-4-{2-[2-(4-methyl-cyclohexyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-cyclopropyl}-phenyl)-methyl-carbamic acid tert-butyl ester. This mixture was used in the next reaction as such without further purification.

Workup

  1. temperaturethe mixture was heated
  2. stirringwith stirring at 50° C. for 15 hours
  3. customAfter returning to room temperature
  4. customThe organic layer and the aqueous layer were separated
  5. extractionthe aqueous layer was repeatedly extracted with ethyl acetate three times
  6. washwashed with water twice
  7. concentrationsaturated brine, and then concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography
  9. customto give
  10. customThis mixture was used in the next reaction as
  11. customsuch without further purification

Sources & evidence

ORD record
ord-caab6bb2f2ee4ca88015f79bf684dd81
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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