Hydrochloric Acid → 7-Amino-2-chloro-8-(2-hydroxy-2-methylpropyl)-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide

HRID 871876Notes

Reaction equation

HRID 871876 reaction equation
[C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[H-].[Na+].[Cl:9][C:10]1[N:15]=[C:14]([NH:16][CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[C:13]([C:22](F)=[O:23])=[CH:12][N:11]=1.Cl>CN(C=O)C.O>[NH2:2][C:1]1[N:16]([CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])[C:14]2[N:15]=[C:10]([Cl:9])[N:11]=[CH:12][C:13]=2[C:22](=[O:23])[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7898CyanoacetamideHCID 24758Sodium hydride2×HCID 891066152-Chloro-4-(2-hydroxy-2-methylpropylamino)pyrimidine-5-carboxylic acid fluoride

Product 1

HCID 866731447-Amino-2-chloro-8-(2-hydroxy-2-methylpropyl)-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamideYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
3.5 °C

Procedure

To a solution, cooled to 2-5°C. on an ice bath, of 4.4 g (52.36 mmol) of cyanoacetamide in 70 mL of anhydrous DMF are added portionwise 4.19 g (104.72 mmol) of 60% sodium hydride. The mixture is stirred for 15 minutes at 2-5°C., and this suspension is then added rapidly to a solution of 12.35 g (49.87 mmol) of the acid fluoride prepared in step 17.2 in 70 mL of anhydrous DMF, precooled to 2-5°C. The mixture is stirred overnight at room temperature and is then cooled to 2-5°C. on an ice bath, and 2.09 g (52.36 mmol) of 60% sodium hydride are added portionwise. The reaction mixture is stirred for 3 hours at room temperature and then poured into a mixture of ice, 100 mL of water and 150 mL of aqueous 1N HCl. The yellow precipitate formed is isolated by filtration, rinsed with water and then dried in an oven. After triturating in methanol and drying in an oven, 8.84 g of the expected product are finally obtained in the form of a yellow solid. Yield=57%.

Workup

  1. customprecooled to 2-5°C
  2. stirringThe mixture is stirred overnight at room temperature
  3. temperatureis then cooled to 2-5°C. on an ice bath
  4. stirringThe reaction mixture is stirred for 3 hours at room temperature
  5. customThe yellow precipitate formed
  6. customis isolated by filtration
  7. washrinsed with water
  8. customdried in an oven
  9. customAfter triturating in methanol
  10. customdrying in an oven

Sources & evidence

ORD record
ord-a10dbece4fff41dd9f3981cb5045a1e7
Source dataset
uspto-grants-2015_03
Patent number
US08975250B2

Reaction notes

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