Cyanoacetamide → tert-Butyl [3-(7-amino-6-carbamoyl-2-chloro-5-oxo-5H-pyrido[2,3-d]pyrimidin-8-yl)propyl]carbamate

HRID 871862Notes

Reaction equation

HRID 871862 reaction equation
[C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[H-].[Na+].[C:9]([O:13][C:14](=[O:30])[NH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]1[C:25]([C:26](F)=[O:27])=[CH:24][N:23]=[C:22]([Cl:29])[N:21]=1)([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14](=[O:30])[NH:15][CH2:16][CH2:17][CH2:18][N:19]1[C:20]2[N:21]=[C:22]([Cl:29])[N:23]=[CH:24][C:25]=2[C:26](=[O:27])[C:3]([C:4](=[O:5])[NH2:6])=[C:1]1[NH2:2])([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 7898CyanoacetamideHCID 24758Sodium hydride2×HCID 86673139tert-Butyl [3-(2-chloro-5-fluorocarbonylpyrimidin-4-ylamino)propyl]-carbamate

Product 1

HCID 86673138tert-Butyl [3-(7-amino-6-carbamoyl-2-chloro-5-oxo-5H-pyrido[2,3-d]pyrimidin-8-yl)propyl]carbamateYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
3.5 °C

Procedure

To a solution, cooled to 2-5°C. on an ice bath, of 1.21 g (14.39 mmol) of cyanoacetamide in 20 mL of anhydrous DMF are added portionwise 1.73 g (43.17 mmol) of 60% sodium hydride. The mixture is stirred for 15 minutes at 2-5°C., and this suspension is then added rapidly to the solution of 4.56 g (13.70 mmol) of the acid fluoride prepared in step 11.2 in 30 mL of anhydrous DMF, precooled to 2-5°C. on an ice bath. The mixture is stirred overnight at room temperature and then cooled to 2-5°C., and a further 0.22 g of 60% sodium hydride is added. The medium is stirred overnight at room temperature, and ice is then added slowly to destroy the excess hydride, and the reaction mixture is poured into an ice-water mixture. The resulting mixture is acidified by adding aqueous 1 N HCl solution. The precipitate formed is isolated by filtration, rinsed with water and then dried. The expected product is obtained in the form of an orange solid, which is used as obtained in the following step. Yield=64%.

Workup

  1. customprecooled to 2-5°C. on an ice bath
  2. stirringThe mixture is stirred overnight at room temperature
  3. temperaturecooled to 2-5°C.
  4. stirringThe medium is stirred overnight at room temperature
  5. additionice is then added slowly
  6. customto destroy the excess hydride
  7. additionthe reaction mixture is poured into an ice-water mixture
  8. additionby adding aqueous 1 N HCl solution
  9. customThe precipitate formed
  10. customis isolated by filtration
  11. washrinsed with water
  12. customdried

Sources & evidence

ORD record
ord-1939cdc1c10a490eb139945ffee42604
Source dataset
uspto-grants-2015_03
Patent number
US08975250B2

Reaction notes

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