L-Proline → HCID 86758297, compound

HRID 2227274Notes

Reaction equation

HRID 2227274 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=O)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:10]([O:12][C:13](=[O:39])[CH:14]([C:31]1[CH:32]=[N:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=1)[CH2:15][CH2:16][CH2:17][CH2:18][N:19]1[CH:23]([CH3:24])[CH2:22][CH:21]([CH2:25][CH2:26][C:27](=O)[CH3:28])[C:20]1=[O:30])[CH3:11].N1CCC[C@H]1C(O)=O.[H][H]>C(O)C.C(OCC)(=O)C.CO.[Pd]>[CH2:10]([O:12][C:13](=[O:39])[CH:14]([C:31]1[CH:32]=[N:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=1)[CH2:15][CH2:16][CH2:17][CH2:18][N:19]1[CH:23]([CH3:24])[CH2:22][C@H:21]([CH2:25][CH2:26][C:27]2[CH:28]=[CH:8][C:7]3[CH2:6][CH2:5][CH2:4][NH:3][C:2]=3[N:1]=2)[C:20]1=[O:30])[CH3:11]

Participants

9

Reactant 4

HCID 145742L-ProlineHCID 7376333-Pyridinecarboxaldehyde, 2-amino-HCID 86758295HCID 86758295, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86758297HCID 86758297, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of 2-amino-3-formylpyridine (341 mg, 2.80 mmol), 3-5 (900 mg, 2.15 mmol) and proline (322 mg, 2.80 mmol) in ethanol (20 mL) was heated at reflux for 4 h, and the cooled to ambient temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The reaction mixture was filtered and concentrated at reduced pressure. The resulting oil was purified by flash column chromatography (silica gel, 3:0.3:0.3 to 8:0.8:0.8% ethanol/ammonium hydroxide/water in ethyl acetate) to give 3-6 as an inseparable mixture of diastereomers. To a stirred solution of the mixture of 3-6 in methanol (40 mL) was added a slurry of 10% palladium on carbon (150 mg) in ethanol (3 mL). The resulting suspension was stirred under a slight overpressure of hydrogen for 16 h. The reaction mixture was filtered through Celite and concentrated at reduced pressure. The resulting oil was purified by flash column chromatography (silica gel, 3:0.3:0.3 to 8:0.8:0.8% ethanol/ammonium hydroxide/water in ethyl acetate) to give 3-7 as a 2:1 mixture of diastereomers.

Workup

  1. temperatureat reflux for 4 h
  2. washwashed with saturated aqueous sodium hydrogen carbonate, saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe reaction mixture was filtered
  5. concentrationconcentrated at reduced pressure
  6. customThe resulting oil was purified by flash column chromatography (silica gel, 3:0.3:0.3 to 8:0.8:0.8% ethanol/ammonium hydroxide/water in ethyl acetate)
  7. customto give 3-6
  8. additionas an inseparable mixture of diastereomers
  9. filtrationThe reaction mixture was filtered through Celite
  10. concentrationconcentrated at reduced pressure
  11. customThe resulting oil was purified by flash column chromatography (silica gel, 3:0.3:0.3 to 8:0.8:0.8% ethanol/ammonium hydroxide/water in ethyl acetate)
  12. customto give 3-7
  13. additionas a 2:1 mixture of diastereomers

Sources & evidence

ORD record
ord-f0f0d16e6d9d472c82963a18f9e1bed5
Source dataset
uspto-grants-2002_07
Patent number
US06413955B1

Reaction notes

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