2-Amino-5-cyanopyridine → HCID 57504747, compound

HRID 1098287Notes

Reaction equation

HRID 1098287 reaction equation
C[Al](C)C.[NH2:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1.[OH:14][C@@H:15]([CH2:20][O:21][C@H:22]([CH3:35])[CH2:23][O:24][Si:25]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])[C:16](OC)=[O:17]>C1(C)C=CC=CC=1>[C:10]([C:9]1[CH:12]=[CH:13][C:6]([NH:5][C:16](=[O:17])[C@@H:15]([OH:14])[CH2:20][O:21][C@H:22]([CH3:35])[CH2:23][O:24][Si:25]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:27])[CH3:28])[CH:32]([CH3:33])[CH3:34])=[N:7][CH:8]=1)#[N:11]

Participants

5

Reactant 3

HCID 8182602-Amino-5-cyanopyridineHCID 16682925TrimethylaluminumHCID 59279456HCID 59279456, compound

Product 1

HCID 57504747HCID 57504747, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (5.98 mL, 11.96 mmol) was added to 6-aminonicotinonitrile (1.424 g, 11.96 mmol) in toluene (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (S)-Methyl 2-hydroxy-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanoate (Intermediate AU5) (2 g, 5.98 mmol) in toluene (6 mL) was added and the reaction was allowed to warm to room temperature and then refluxed for 6 hours. The reaction mixture was allowed to cool and concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water (25 mL) and extracted with EtOAc (2×50 mL). The combined organics were washed with brine (20 mL), then dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (1.760 g, 69.8%).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 6 hours
  3. temperatureto cool
  4. concentrationconcentrated in vacuo
  5. additiondiluted with water (25 mL)
  6. extractionextracted with EtOAc (2×50 mL)
  7. washThe combined organics were washed with brine (20 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with 30 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-761edcb9986940af8bc5ed90867a7c67
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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