2-Amino-5-cyanopyridine → HCID 57504560, compound

HRID 1098253Notes

Reaction equation

HRID 1098253 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][CH2:22][CH2:23][CH2:24][C@H:25]([O:30][C:31]1[N:36]=[CH:35][N:34]=[C:33]2[N:37]([C:40]3[C:45]([Cl:46])=[CH:44][CH:43]=[CH:42][N:41]=3)[N:38]=[CH:39][C:32]=12)[C:26](OC)=[O:27])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1(C)C=CC=CC=1>[Si:14]([O:21][CH2:22][CH2:23][CH2:24][C@H:25]([O:30][C:31]1[N:36]=[CH:35][N:34]=[C:33]2[N:37]([C:40]3[C:45]([Cl:46])=[CH:44][CH:43]=[CH:42][N:41]=3)[N:38]=[CH:39][C:32]=12)[C:26]([NH:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1)=[O:27])([C:17]([CH3:19])([CH3:20])[CH3:18])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 8182602-Amino-5-cyanopyridineHCID 16682925TrimethylaluminumHCID 57504618HCID 57504618, compound

Product 1

HCID 57504560HCID 57504560, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of trimethylaluminium (2M in toluene) (0.795 mL, 1.59 mmol) was added dropwise to a stirred solution of 6-aminonicotinonitrile (165 mg, 1.38 mmol) in toluene (5 mL) cooled to 0° C., over a period of 1 minute under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. A solution of (2S)-methyl 5-(tert-butyldimethylsilyloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanoate (Intermediate O2) (680 mg, 1.38 mmol) in toluene (5 mL) was added dropwise. The resulting solution was stirred at 0° C. for 10 minutes allowed to warm to ambient temperature and then heated at reflux for 18 hours. The reaction mixture was allowed to cool to r.t. and concentrated. The residue was diluted with ethyl acetate and treated with 1M citric acid (2 ml). The layers were separated and the organics were washed with water and brine, dried (MgSO4) and evaporated to afford the product (797 mg) which was used without further purification. m/z (ES−) (M−H)−=577.45; HPLC tR=3.29 min.

Workup

  1. stirringThe resulting solution was stirred at 0° C. for 10 minutes
  2. temperatureto warm to ambient temperature
  3. temperatureheated
  4. temperatureat reflux for 18 hours
  5. temperatureto cool to r.t.
  6. concentrationconcentrated
  7. additionThe residue was diluted with ethyl acetate
  8. additiontreated with 1M citric acid (2 ml)
  9. customThe layers were separated
  10. washthe organics were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. customevaporated

Sources & evidence

ORD record
ord-31bdf464ff5046bab133f9030ccc919e
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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