Acetyl chloride → HCID 178473989, compound

HRID 1269941Notes

Reaction equation

HRID 1269941 reaction equation
[C:1]1(=[O:7])[O:6][C:4](=O)[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl.[CH3:16][C:17]1[C:25]([O:26][C@@H:27]2[CH2:32][CH2:31][C@H:30]([NH2:33])[CH2:29][CH2:28]2)=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[N:20][NH:21]2.[C:34](Cl)(=[O:36])[CH3:35]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CN(C)C=O.O>[C:34]([N:21]1[C:22]2[C:18](=[C:17]([CH3:16])[C:25]([O:26][C@@H:27]3[CH2:32][CH2:31][C@H:30]([N:33]4[C:1](=[O:7])[CH2:2][CH2:3][C:4]4=[O:6])[CH2:29][CH2:28]3)=[CH:24][CH:23]=2)[CH:19]=[N:20]1)(=[O:36])[CH3:35]

Participants

9

Reactant 4

HCID 6367Acetyl chlorideHCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 178431637HCID 178431637, compound

Product 1

HCID 178473989HCID 178473989, compoundYield 33.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, succinic anhydride (105 mg, 1.05 mmol) and triethylamine (279 μl, 2.00 mmol) were added to a solution of the cis-4-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanamine hydrochloride (282 mg, 1.00 mmol) obtained in Example 410 in toluene (6 ml) at room temperature, and the resulting mixture was refluxed. After 5.5 hours, the reaction solution was poured into water and extracted with ethyl acetate. The extract solution was concentrated under reduced pressure, and to a solution of the resulting residue in ethyl acetate (4 ml) was added acetyl chloride (214 μl, 3.00 mmol), and the resulting mixture was heated to 100° C. Dimethylformamide (2 ml) was added thereto because a solid was precipitated. After 2 hours, the reaction solution was poured into water and extracted with ethyl acetate. The extract solution was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain cis-1-{4-[(1-acetyl-4-methyl-1H-indazol-5-yl)oxy]cyclohexyl}pyrrolidine-2,5-dione (123.7 mg, 33%).

Workup

  1. temperaturethe resulting mixture was refluxed
  2. extractionextracted with ethyl acetate
  3. concentrationThe extract solution was concentrated under reduced pressure
  4. custombecause a solid was precipitated
  5. waitAfter 2 hours
  6. additionthe reaction solution was poured into water
  7. extractionextracted with ethyl acetate
  8. concentrationThe extract solution was concentrated under reduced pressure
  9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3097df2e139a4aa3a5d78e54cf8f20c2
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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