Hydrochloric Acid → HCID 22184425, compound

HRID 1795010Notes

Reaction equation

HRID 1795010 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][O:11][C:10]2[N:15]=[C:16](Cl)[CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]=2[C:8]1=[O:27].C([O:41][C:42]([N:44]1[CH2:50][CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)=O)(C)(C)C.Cl.[C:52](OC(=O)C)(=O)C>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[C:42]([N:44]1[CH2:50][CH2:49][CH2:48][N:47]([C:16]2[CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]3[C:8](=[O:27])[N:7]([CH2:6][C:5]4[CH:4]=[C:3]([C:2]([F:36])([F:35])[F:1])[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=4)[CH2:14][CH2:13][CH2:12][O:11][C:10]=3[N:15]=2)[CH2:46][CH2:45]1)(=[O:41])[CH3:52]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 22179334HCID 22179334, compound

Product 1

HCID 22184425HCID 22184425, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
150 °C

Procedure

A mixture of 5-[3,5-bis(trifluoromethyl)benzyl]-9-chloro-7-(2-methylphenyl)-6-oxo-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (compound of Reference Example 17; 100 mg) and 1-(t-butoxycarbonyl)homopiperazine (95.0 mg) was stirred at 150° C. for 5 hours. While the resulting residue was chilled on an ice bath, a 3 mol/L ethyl acetate solution of hydrogen chloride (1 mL) was added, and then the mixture was stirred at room temperature for 1 hour. The solvent was removed by distillation to obtain a residue, and then the residue was dissolved in tetrahydrofuran (1 mL). While the resulting solution was chilled on an ice bath, triethylamine (0.2 mL) and acetic anhydride (0.1 mL) were added, and then the mixture was stirred for 1 hour. To the reaction mixture, ethyl acetate was added. The resulting mixture was washed with water, and was then dried on anhydrous sodium sulfate. The solvent was removed by distillation to obtain a residue, and then the residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1) to obtain 9-(4-acetylhomopiperazine-1-yl)-5-[3,5-bis(trifluoromethyl)benzyl]-7-(2-methylphenyl)-6-oxo-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (42.7 mg, 36%).

Workup

  1. temperatureWhile the resulting residue was chilled on an ice bath
  2. stirringthe mixture was stirred at room temperature for 1 hour
  3. customThe solvent was removed by distillation
  4. customto obtain a residue
  5. temperatureWhile the resulting solution was chilled on an ice bath
  6. stirringthe mixture was stirred for 1 hour
  7. washThe resulting mixture was washed with water
  8. dry with materialwas then dried on anhydrous sodium sulfate
  9. customThe solvent was removed by distillation
  10. customto obtain a residue
  11. customthe residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-538895a89ada47799e8bbd75d1b7a095
Source dataset
uspto-grants-2006_04
Patent number
US07026309B2

Reaction notes

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