Acetic Acid → HCID 66973402, compound

HRID 1502596Notes

Reaction equation

HRID 1502596 reaction equation
[N:1]1[CH:6]=[C:5]([CH:7]=O)[CH:4]=[N:3][CH:2]=1.[NH2:9][C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][N:11]=1.[BH4-].[Na+].C(O)(=O)C>C1(C)C=CC=CC=1.CO.O>[N:1]1[CH:6]=[C:5]([CH2:7][NH:9][C:10]2[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:4]=[N:3][CH:2]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 153472-Amino-3-methylpyridineHCID 2761034Pyrimidine-5-carboxaldehydeHCID 4311764Sodium borohydride2×

Product 1

HCID 66973402HCID 66973402, compoundYield 96.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 5-pyrimidinecarboxaldehyde (5.0 g, 46 mmol) in toluene (100 mL) was added 2-amino-3-picoline (5.0 g, 46 mmol). The reaction mixture was heated to 80° C. on a rotary evaporator while under reduced pressure. After 10 min an additional 200 mL of toluene was added. Continued heating under reduced pressure resulted in a white solid which was dissolved in methanol (200 mL). This solution was stirred vigorously under a nitrogen atmosphere, and granular sodium borohydride (10.0 g, 265 mmol) was added portionwise, resulting in vigorous bubbling. The reaction was allowed to stir for 1 h at room temperature after completion of the sodium borohydride addition. Acetic acid (1 mL) was then added, and the reaction mixture was stirred for 5 min, followed by the addition of water (100 mL). The volatiles were removed under reduced pressure, and the aqueous suspension was extracted with dichloromethane (2×100 mL). The organic layers were combined and dried over MgSO4, filtered, and the solvent was removed under reduced pressure to yield an off-white solid. The crude solid was adsorbed onto Celite® and purified by column chromatography (gradient of 100% hexanes to 100% ethyl acetate over 30 minutes) to yield 8.848 g of a white solid.

Workup

  1. temperatureContinued heating under reduced pressure
  2. customresulted in a white solid which
  3. customresulting in vigorous bubbling
  4. stirringto stir for 1 h at room temperature
  5. stirringthe reaction mixture was stirred for 5 min
  6. customThe volatiles were removed under reduced pressure
  7. extractionthe aqueous suspension was extracted with dichloromethane (2×100 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvent was removed under reduced pressure
  11. customto yield an off-white solid
  12. custompurified by column chromatography (gradient of 100% hexanes to 100% ethyl acetate over 30 minutes)

Sources & evidence

ORD record
ord-54e3bd9ce8374bbfb2b52d89c4497432
Source dataset
uspto-grants-2015_12
Patent number
US09210932B2

Reaction notes

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