1,4-Dioxane → HCID 22053578, compound

HRID 1829669Notes

Reaction equation

HRID 1829669 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[F:19][C:20]([F:57])([F:56])[C:21]1[CH:22]=[C:23]([CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=1)[CH2:24][N:25]1[CH2:32][CH2:31][CH2:30][NH:29][C:28]2[N:33]=[C:34](S(C)(=O)=O)[N:35]=[C:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[CH3:43])[C:27]=2[C:26]1=[O:48].[O:58]1CCO[CH2:60][CH2:59]1>>[C:59]([N:29]1[CH2:30][CH2:31][CH2:32][N:25]([CH2:24][C:23]2[CH:49]=[C:50]([C:52]([F:54])([F:53])[F:55])[CH:51]=[C:21]([C:20]([F:57])([F:19])[F:56])[CH:22]=2)[C:26](=[O:48])[C:27]2[C:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[CH3:43])=[N:35][C:34]([N:7]3[CH2:8][CH2:9][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]3)=[N:33][C:28]1=2)(=[O:58])[CH3:60]

Participants

5

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 837951-AcetylpiperazineHCID 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 22053578HCID 22053578, compoundYield 91%

Conditions

Temperature
100 °C

Procedure

1-acetylpiperazine (23.1 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 solvent was removed and anhydrous acetic acid (0.5 mL) and pyridine (0.1 mL) were added, followed by stirring at 100° C. for 3 hours. Subsequently, the reaction mixture was diluted with ethyl acetate, was sequentially washed with water and a saturated aqueous solution of sodium chloride, 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 10-acetyl-2-(4-acetylpiperazine-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 (90.2 mg, 91%).

Workup

  1. temperatureWhile heated
  2. temperaturethe mixture was refluxed for 5 hours
  3. customThe solvent was removed
  4. additionanhydrous acetic acid (0.5 mL) and pyridine (0.1 mL) were added
  5. additionSubsequently, the reaction mixture was diluted with ethyl acetate
  6. washwas sequentially washed with water
  7. dry with materiala saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate
  8. customremoval of the solvent
  9. customthe residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-637c6e824d044429badc18dee0ece630
Source dataset
uspto-grants-2006_06
Patent number
US07064119B2

Reaction notes

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