proline dl-form → HCID 58392315, compound

HRID 561404Notes

Reaction equation

HRID 561404 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=O.C[C:15]1([CH3:23])[O:22][C:20](=[O:21])[CH2:19]C(=O)O1.N1CCCC1C(O)=O.[CH3:32][S:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:43]=1[NH:42][CH:41]=[CH:40]2>C(#N)C.[Cu].C(O)C.N1C=CC=CC=1>[F:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]([C:40]1[C:39]2[C:43](=[C:35]([CH2:34][S:33][CH3:32])[CH:36]=[CH:37][CH:38]=2)[NH:42][CH:41]=1)[CH2:19][C:20]([O:22][CH2:15][CH3:23])=[O:21]

Participants

9

Reactant 4

HCID 614proline dl-formHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 5229292-Fluoro-4-(trifluoromethyl)benzaldehydeHCID 583921877-[(Methylsulfanyl)methyl]-1H-indole

Product 1

HCID 58392315HCID 58392315, compound

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 702EthanolSolventHCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

1.54 g (8.00 mmol) of 2-fluoro-4-(trifluoromethyl)benzaldehyde, 1.15 g (8.00 mmol) of Meldrum's acid and 44 mg (0.38 mmol) of D,L-proline were added to a solution of 1.50 g (7.62 mmol) of the compound from Example 8A in 62 ml of acetonitrile. The reaction mixture was stirred at RT overnight. It was concentrated to result in 4.47 g of a crude product which was introduced into 48 ml of pyridine and 12 ml of ethanol, and 4 mg (63 μmol) of copper powder were added. The reaction mixture was heated under reflux for 1 h. It was concentrated, and 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 2.74 g (82% of theory) of the title compound.

Workup

  1. concentrationIt was concentrated
  2. customto result in 4.47 g of a crude product which
  3. additionwere added
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 1 h
  6. concentrationIt was concentrated
  7. 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-2e349945e8b24e64a2f18dbb7ea3b454
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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