Hydrochloric Acid → HCID 86673132, compound

HRID 871846Notes

Reaction equation

HRID 871846 reaction equation
[C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[H-].[Na+].[Cl:9][C:10]1(C(F)=O)[N:15]=[C:14]([NH:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:13]=[CH:12][NH:11]1.Cl.CN([CH:29]=[O:30])C>O>[NH2:2][C:1]1[N:16]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)[C:14]2[N:15]=[C:10]([Cl:9])[N:11]=[CH:12][C:13]=2[C:29](=[O:30])[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228Dimethylformamide2×HCID 7898CyanoacetamideHCID 24758Sodium hydride2×HCID 178521536HCID 178521536, compound

Product 1

HCID 86673132HCID 86673132, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
3.5 °C

Procedure

To a solution, cooled to 2-5°C. on an ice bath, of 1.88 g (22.41 mmol) of cyanoacetamide in 20 mL of anhydrous DMF are added portionwise 1.8 g (44.82 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 5.2 g (21.34 mmol) of the acid fluoride prepared in step 3.2 in 20 mL of anhydrous DMF precooled to 2-5°C. The mixture is stirred overnight at room temperature and then cooled to 2-5°C. on an ice bath, and 0.90 g (22.41 mmol) of 60% sodium hydride is 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 which it is rinsed with pentane. 5.4 g of a mixture containing the expected cyclized product and the non-cyclized product are finally obtained in the form of an orange powder. The mixture is purified by chromatography on a column of silica, eluting with a dichloromethane/methanol gradient (99/1 to 96/4). 0.6 g of the expected product is finally obtained in the form of a pale yellow solid. Yield=9%.

Workup

  1. customprecooled to 2-5°C
  2. stirringThe mixture is stirred overnight at room temperature
  3. temperaturecooled 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. washafter which it is rinsed with pentane
  10. addition5.4 g of a mixture containing the expected cyclized product
  11. customthe non-cyclized product are finally obtained in the form of an orange powder
  12. customThe mixture is purified by chromatography on a column of silica
  13. washeluting with a dichloromethane/methanol gradient (99/1 to 96/4)

Sources & evidence

ORD record
ord-eafd4143468d4c4e8eb8fb9e08ceaeac
Source dataset
uspto-grants-2015_03
Patent number
US08975250B2

Reaction notes

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