proline dl-form → HCID 58392275, compound

HRID 561403Notes

Reaction equation

HRID 561403 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([CH3:10])[CH:3]=1.C[C:12]1([CH3:20])[O:19][C:17](=[O:18])[CH2:16]C(=O)O1.N1CCCC1C(O)=O.[CH3:29][S:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:40]=1[NH:39][CH:38]=[CH:37]2>C(#N)C.[Cu].C(O)C.N1C=CC=CC=1>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([C:37]2[C:36]3[C:40](=[C:32]([CH2:31][S:30][CH3:29])[CH:33]=[CH:34][CH:35]=3)[NH:39][CH:38]=2)[CH2:16][C:17]([O:19][CH2:12][CH3:20])=[O:18])=[C:4]([CH3:10])[CH:3]=1

Participants

9

Reactant 4

HCID 614proline dl-formHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 27576584-Chloro-2-methylbenzaldehydeHCID 583921877-[(Methylsulfanyl)methyl]-1H-indole

Product 1

HCID 58392275HCID 58392275, compound

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 702EthanolSolventHCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

1.44 g (9.31 mmol) of 4-chloro-2-methylbenzaldehyde, 1.34 g (9.31 mmol) of Meldrum's acid and 48.7 mg (0.42 mmol) of D,L-proline were added to a solution of 1.50 g (8.46 mmol) of the compound from Example 8A in 70 ml of acetonitrile. The reaction mixture was stirred at RT overnight. It was concentrated, and the residue was taken up in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. 3.43 g of a crude product were obtained and were introduced into 53 ml of pyridine and 14 ml of ethanol, and 4.8 mg (75 μmol) of copper powder were added. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was taken up in ethyl acetate, washed with 1N hydrochloric acid, dried over magnesium sulfate, filtered through silica gel and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 1.68 g (49% of theory) of the title compound.

Workup

  1. concentrationIt was concentrated
  2. washwashed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custom3.43 g of a crude product were obtained
  7. additionwere added
  8. temperatureThe reaction mixture was heated
  9. temperatureunder reflux for 1 h
  10. concentrationIt was concentrated
  11. washwashed with 1N hydrochloric acid
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered through silica gel
  14. concentrationconcentrated
  15. customThe crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-b998de4b46d24570b1c7ab418e38e89f
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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