1,4-Dioxane → HCID 22053589, compound

HRID 1829670Notes

Reaction equation

HRID 1829670 reaction equation
C(O[C:6]([N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])(C)(C)C.[CH:15](N(C(C)C)CC)(C)C.O1CCOCC1.[F:30][C:31]([F:68])([F:67])[C:32]1[CH:33]=[C:34]([CH:60]=[C:61]([C:63]([F:66])([F:65])[F:64])[CH:62]=1)[CH2:35][N:36]1[CH2:43][CH2:42][CH2:41][NH:40][C:39]2[N:44]=[C:45](S(C)(=O)=O)[N:46]=[C:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[CH3:54])[C:38]=2[C:37]1=[O:59]>C(OCC)(=O)C>[C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:45]2[N:46]=[C:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[CH3:54])[C:38]3[C:37](=[O:59])[N:36]([CH2:35][C:34]4[CH:60]=[C:61]([C:63]([F:66])([F:65])[F:64])[CH:62]=[C:32]([C:31]([F:30])([F:68])[F:67])[CH:33]=4)[CH2:43][CH2:42][CH2:41][NH:40][C:39]=3[N:44]=2)[CH2:10][CH2:9]1)(=[O:7])[CH3:15]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 220535916-[3,5-Bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-2-(methylsulfonyl)-5-oxopyrimido[4,5-b][1,5]diazocine

Product 1

HCID 22053589HCID 22053589, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1-(t-butoxycarbonyl)homopiperazine (36.1 mg), diisopropylethylamine (0.1 mL) and 1,4-dioxane (1 mL) were added to 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-2-(methylsulfonyl)-5-oxopyrimido[4,5-b][1,5]diazocine (Compound of Reference Example 19; 85.9 mg). While heated, the mixture was refluxed for 5 hours. The reaction mixture was then diluted with ethyl acetate, was washed with water, and was then dried over anhydrous sodium sulfate. The solvent was removed and 3 mol/L hydrogen chloride/ethyl acetate (1 mL) was added while the residue was chilled on an ice bath. The mixture was stirred for 30 min and then additional 1 hour at room temperature. Following removal of the solvent, the residue was dissolved in tetrahydrofuran (1 mL). While the residue was chilled on an ice bath, triethylamine (0.1 mL) and anhydrous acetic acid (0.05 mL) were added and the mixture was stirred at room temperature for 30 min. Subsequently, the reaction mixture was diluted with ethyl acetate, was washed with water, and was then dried over anhydrous sodium sulfate. Following removal of the solvent, the residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1) to obtain 2-(4-acetylhomopiperazine-1-yl)-6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-5-oxopyrimido[4,5-b][1,5]diazocine (70.7 mg, 74%).

Workup

  1. temperatureWhile heated
  2. temperaturethe mixture was refluxed for 5 hours
  3. washwas washed with water
  4. dry with materialwas then dried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. addition3 mol/L hydrogen chloride/ethyl acetate (1 mL) was added while the residue
  7. temperaturewas chilled on an ice bath
  8. customadditional 1 hour
  9. customat room temperature
  10. customremoval of the solvent
  11. dissolutionthe residue was dissolved in tetrahydrofuran (1 mL)
  12. temperatureWhile the residue was chilled on an ice bath
  13. additiontriethylamine (0.1 mL) and anhydrous acetic acid (0.05 mL) were added
  14. stirringthe mixture was stirred at room temperature for 30 min
  15. additionSubsequently, the reaction mixture was diluted with ethyl acetate
  16. washwas washed with water
  17. dry with materialwas then dried over anhydrous sodium sulfate
  18. customremoval of the solvent
  19. customthe residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-a0f77c24a89d4246b819ba2e7efdebd5
Source dataset
uspto-grants-2006_06
Patent number
US07064119B2

Reaction notes

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