Acetyl chloride → 7-acetyl-10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

HRID 1753127Notes

Reaction equation

HRID 1753127 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[NH:20][CH2:19][CH2:18][N:9]2[C:10](=[O:17])[C:11]2[N:12]([CH:14]=[CH:15][CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:25](Cl)(=[O:27])[CH3:26]>ClCCCl.C([O-])(O)=O.[Na+]>[C:25]([C:15]1[CH:16]=[C:11]2[C:10](=[O:17])[N:9]3[CH2:18][CH2:19][NH:20][C:8]3([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH2:13][N:12]2[CH:14]=1)(=[O:27])[CH3:26]

Participants

6

Reactant 3

HCID 6367Acetyl chloride3×HCID 6451240Aluminum(III) Chloride2×HCID 6736965310a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

Product 1

HCID 673788247-acetyl-10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-oneYield 41%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (50 mg, 0.17 mmol) and aluminium chloride (53 mg, 0.40 mmol) were suspended in 1,2-dichloroethane (1 mL). Acetyl chloride (15 μL, 0.21 mmol) in 1,2-dichloroethane was added dropwise to the reaction mixture. After 16 h at room temperature the reaction was not completed and another portion of acetyl chloride (15 μL, 0.21 mmol) was added. The reaction was still incomplete after a further 6 h at room temperature, therefore further acetyl chloride (15 μL, 0.21 mmol) and aluminium chloride (53 mg) were added and the reaction mixture was heated at 60° C. for 2 h. LCMS analysis showed a large amount of doubly acetylated product (372 m/z), along with target product (330 m/z) and a smaller amount of starting material (288 m/z). The reaction mixture was diluted with saturated aqueous solution of NaHCO3 (25 mL) and extracted with CH2Cl2 containing 20% of propan-2-ol (2×25 mL). The organic layers were combined, dried and concentrated in vacuo to give a brown oil. The crude mixture was purified using flash chromatography (Biotage SP4, 12 g cartridge, 0-20% MeOH gradient in CH2Cl2′) to give 7-acetyl-10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (23 mg, 40% yield). ESI-MI m/z [M+H]+ 329.9.

Workup

  1. waitThe reaction was still incomplete after a further 6 h at room temperature
  2. extractionextracted with CH2Cl2 containing 20% of propan-2-ol (2×25 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customto give a brown oil
  6. customThe crude mixture was purified

Sources & evidence

ORD record
ord-b93c3490cffd4b29ab20a211e6bfaa06
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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