4-Methylmorpholine → N-[5-Bromo-2-chloro-4-(ethylamino)-3-pyridinyl]-2-cyanoacetamide

HRID 1863996Notes

Reaction equation

HRID 1863996 reaction equation
[Br:1][C:2]1[C:3]([NH:10][CH2:11][CH3:12])=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.Cl.CN(C)CCCN=C=NCC.[C:25]([CH2:27][C:28](O)=[O:29])#[N:26].CN1CCOCC1>C(Cl)Cl>[Br:1][C:2]1[C:3]([NH:10][CH2:11][CH3:12])=[C:4]([NH:9][C:28](=[O:29])[CH2:27][C:25]#[N:26])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9740Cyanoacetic acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 45480182HCID 45480182, compound

Product 1

HCID 57973904N-[5-Bromo-2-chloro-4-(ethylamino)-3-pyridinyl]-2-cyanoacetamideYield 76.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-bromo-2-chloro-N4-ethyl-pyridine-3,4-diamine (II, 550 g, 2.21 mol) in CH2Cl2 (5.5 L) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (634.5 g, 3.31 mol), cyanoacetic acid (282 g, 3.31 mol) and N-methylmorpholine (897 g, 8.84 mol). A significant exotherm (˜20° C.) was observed upon the addition of the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and cyanoacetic acid. After stirring at ambient temperature for 2 h, the solvent was removed under reduced pressure. The resulting reside was extracted with warm EtOAc (40° C., 20 L) and water (40° C., 8 L). The aqueous layer was washed with addition EtOAc (10 L) and the combined organic extracts were washed with water (10 L). The organic extract was concentrated under reduced pressure to a slurry and filtered. The solid was washed with EtOAc and dried to give 534 g (76% yield) of the desired compound (III) as a white crystalline solid. This was used in the next step without further purification. MS (ES+) m/z 317 (M+H)+.

Workup

  1. customthe solvent was removed under reduced pressure
  2. extractionThe resulting reside was extracted with warm EtOAc (40° C., 20 L) and water (40° C., 8 L)
  3. washThe aqueous layer was washed with addition EtOAc (10 L)
  4. washthe combined organic extracts were washed with water (10 L)
  5. extractionThe organic extract
  6. concentrationwas concentrated under reduced pressure to a slurry
  7. filtrationfiltered
  8. washThe solid was washed with EtOAc
  9. customdried

Sources & evidence

ORD record
ord-2f806903e570408b82673e6dda5e823d
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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