p-Toluenesulfonic acid → (4-amino-6-methyl-2,3-dihydro-1H-8-thia-7-aza-cyclopenta[a]inden-5-yl)-cyclopropyl-methanone

HRID 133543

Reaction equation

HRID 133543 reaction equation
[NH2:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][C:4]=2[C:3]=1[C:10]#[N:11].[CH:12]1([C:15](=[O:21])[CH:16]=[C:17](OC)[CH3:18])[CH2:14][CH2:13]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Sn](Cl)(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:11][C:10]1[C:3]2[C:4]3[CH2:9][CH2:8][CH2:7][C:5]=3[S:6][C:2]=2[N:1]=[C:17]([CH3:18])[C:16]=1[C:15]([CH:12]1[CH2:14][CH2:13]1)=[O:21]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 24287Tin tetrachlorideHCID 2581822-amino-4H,5H,6H-cyclopenta(b)thiophene-3-carbonitrileHCID 688996081-Cyclopropyl-3-methoxy-but-2-en-1-one

Product 1

HCID 68896523(4-amino-6-methyl-2,3-dihydro-1H-8-thia-7-aza-cyclopenta[a]inden-5-yl)-cyclopropyl-methanoneYield 5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 0.30 g (1.83 mmol) of 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile in 6 ml toluene was added 0.30 g (2.14 mmol) 1-cyclopropyl-3-methoxy-but-2-en-1-one and 3 mg of p-toluenesulfonic acid. The mixture was heated at reflux for 2 hours, concentrated in vacuo, partitioned between ethyl acetate and water. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The residue was taken up in n-butyl acetate 6 ml and 1.018 g (3.91 mmol) tin (IV) chloride was heated under reflux for 30 minute and allowed to cool. The mixture was partitioned between aqueous sodium hydroxide and ethyl acetate. Flash chromatography (heptane/ethyl acetate 3:1) afforded 25 mg (5%) (4-amino-6-methyl-2,3-dihydro-1H-8-thia-7-aza-cyclopenta[a]inden-5-yl)-cyclopropyl-methanone as a white solid. ES-MS m/e (%): 273 (M+H+, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 hours
  3. concentrationconcentrated in vacuo
  4. custompartitioned between ethyl acetate and water
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. customevaporated to dryness
  7. temperatureunder reflux for 30 minute
  8. temperatureto cool
  9. customThe mixture was partitioned between aqueous sodium hydroxide and ethyl acetate

Sources & evidence

ORD record
ord-9c25546f3df240cdb6cad1c6fefddfc2
Source dataset
uspto-grants-2008_06
Patent number
US07390903B2

Linked notes

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