2-Amino-5-cyanopyridine → (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-cyanopyridin-2-yl)-2-hydroxypropanamide

HRID 1098272Notes

Reaction equation

HRID 1098272 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.[Si:14]([O:21][CH:22]1[CH2:25][N:24]([CH2:26][C@H:27]([OH:32])[C:28](OC)=[O:29])[CH2:23]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1(C)C=CC=CC=1>[Si:14]([O:21][CH:22]1[CH2:25][N:24]([CH2:26][C@H:27]([OH:32])[C:28]([NH:5][C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=2)=[O:29])[CH2:23]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 8182602-Amino-5-cyanopyridine2×HCID 16682925TrimethylaluminumHCID 57504648(S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate

Product 1

HCID 57504736(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-cyanopyridin-2-yl)-2-hydroxypropanamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (7.95 mL, 15.89 mmol) was added to 6-aminonicotinonitrile (1.646 g, 13.82 mmol) in toluene (50 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-Methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (4.0 g, 13.82 mmol) in toluene (20 mL) was added and the resulting solution was allowed to warm to room temperature and then heated at 60° C. for 3 hours. The mixture was cooled to ˜10° C. and quenched by the addition of 20% Rochelle salt solution. It was then diluted with EtOAc (50 mL) and stirred for 2 hours. The organic phase was separated, washed with water and brine, dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography on silica with EtOAc as eluent to afford the product containing some 6-aminonicotinonitrile (4.1 g). This was used without further purification.

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated at 60° C. for 3 hours
  3. temperatureThe mixture was cooled to ˜10° C.
  4. customquenched by the addition of 20% Rochelle salt solution
  5. additionIt was then diluted with EtOAc (50 mL)
  6. stirringstirred for 2 hours
  7. customThe organic phase was separated
  8. washwashed with water and brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by flash chromatography on silica with EtOAc as eluent
  13. customto afford the product
  14. customThis was used without further purification

Sources & evidence

ORD record
ord-8366d5cbdf7f4d3bbd258dfb9a4daa9a
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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