Triethylamine → Ica-069673

HRID 1271121Notes

Reaction equation

HRID 1271121 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(N(CC)CC)C.[F:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[F:26])[C:20](Cl)=[O:21]>C1COCC1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:20](=[O:21])[C:19]2[CH:23]=[CH:24][C:25]([F:26])=[C:17]([F:16])[CH:18]=2)=[CH:3][N:4]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27245193,4-Difluorobenzoyl chlorideHCID 122159932-Chloropyrimidin-5-amine

Product 1

HCID 10149311Ica-069673Yield 61.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 450 g (3.49 mol) of 5-amino-2-chloropyrimidine and 790 g (6.98 mol) of triethylamine in anhydrous THF was cooled to less than 5° C. in an ice bath. To this solution was added 3,4-difluorobenzoyl chloride at a rate (2 h) that maintained the temperature of the reaction mixture below 10° C. Once the addition was complete the reaction was monitored for full conversion of the starting material to product by HPLC. Following confirmation of complete conversion, the reaction mixture was concentrated under reduced pressure. The viscous residue was dissolved in ethyl acetate (4 L) and washed with water (4 L) and 2M HCl (4 L). The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was dissolved in ethanol (4 L) and 250 g of charcoal was added. The mixture was heated to reflux for 10 minutes and filtered through a bed of Celite® and the filtrate was concentrated under reduced pressure. The solids were recrystallized twice from acetonitrile (1 L) to yield 580 g (61.8%) of the desired product as an off-white solid.

Workup

  1. temperaturemaintained the temperature of the reaction mixture below 10° C
  2. additionOnce the addition
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. dissolutionThe viscous residue was dissolved in ethyl acetate (4 L)
  5. washwashed with water (4 L) and 2M HCl (4 L)
  6. customThe organic layer was separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe resulting solid was dissolved in ethanol (4 L)
  11. addition250 g of charcoal was added
  12. temperatureThe mixture was heated
  13. temperatureto reflux for 10 minutes
  14. filtrationfiltered through a bed of Celite®
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. customThe solids were recrystallized twice from acetonitrile (1 L)

Sources & evidence

ORD record
ord-8abb5f88119546ee92c0e7cf90829127
Source dataset
uspto-grants-2007_04
Patent number
US07205307B2

Reaction notes

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