Pyridine → HCID 86636441, compound

HRID 1471555Notes

Reaction equation

HRID 1471555 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][NH:11][C:12]1[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:13]=1[C:14]([NH2:16])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[CH2:1]([O:8][CH2:9][CH2:10][NH:11][C:12]1[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:13]=1[C:14]#[N:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 57969017HCID 57969017, compound

Product 1

HCID 86636441HCID 86636441, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 2-(2-benzyloxy-ethylamino)-6-chloro-nicotinamide (3, 15.8 g, 51.7 mmol) in acetonitrile (anhydrous, 200 mL) were added pyridine (33.4 mL, 413 mmol) and POCl3 (18.9 mL, 207 mmol). The reaction was heated at 55° C. for 3 hours. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (200 mL) was added and layers separated. The aqueous layer was extracted with EtOAc (2×200 mL). The combined organic layer was dried over MgSO4, filtered, and evaporated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 2%-20% EtOAc/hexanes gradient, to afford 10 g (67% yield) of the title product.

Workup

  1. temperatureAfter cooling to room temperature
  2. customlayers separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification
  8. washeluting with 2%-20% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-95f6f35224dd4f9dac02c0c4c64f6af2
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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