Cyanoacetic acid → 6-Amino-1-(2-methylallyl)pyrimidine-2,4(1H,3H)-dione

HRID 900696Notes

Reaction equation

HRID 900696 reaction equation
[CH3:1][C:2](=[CH2:8])[CH2:3][NH:4][C:5]([NH2:7])=[O:6].[C:9]([CH2:11][C:12](O)=[O:13])#[N:10]>C(OC(=O)C)(=O)C.CCOCC>[NH2:10][C:9]1[N:4]([CH2:3][C:2]([CH3:1])=[CH2:8])[C:5](=[O:6])[NH:7][C:12](=[O:13])[CH:11]=1

Participants

5

Reactant 2

HCID 9740Cyanoacetic acidHCID 22226516(2-Methylallyl)urea

Product 1

HCID 222265436-Amino-1-(2-methylallyl)pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
70 °C

Procedure

Methallylamine (211 g, 2.97 mol) is added to a solution of concentrated hydrochloric acid (250 ml) in water (1.9 l), followed by portionwise addition of potassium cyanate (240 g, 2.97 mol). The reaction is then heated for 2 hours at 80° C., prior to cooling and evaporation to afford (2-methyl-allyl)-urea (2445 g), mp 114-115° C. The urea (268 g, 2.35 mol) is added to a solution of cyanoacetic acid (220 g, 2.59 mol) in acetic anhydride, (536 ml) and the reaction is heated at 70° C. for 1 hour, cooled to 0° C. and diluted with ether. The resultant solid is collected by filtration, washed with ether, suspended in water (2.2 l) and heated to 75° C. 2M aqueous sodium hydroxide solution is then added portionwise over 30 min to maintain pH between 8 and 9.5. The reaction is cooled to room temperature, treated with acetic acid (12 ml), further cooled to 10° C. and the resultant solid is collected by filtration, washed with cold water and dried to afford 6-amino-1-(2-methyl-allyl)-1H-pyrimidine-2,4-dione, mp 267-269° C. The uracil (253 g, 1.40 mol) is added to a solution of sodium hydroxide (123 g, 3.07 mol) in water (2.5 l) and allowed to exotherm then cooled to 20° C. Dimethyl sulfate (196 ml, 2.06 mol) is added portionwise over 1 hour. After standing overnight, the reaction is cooled to 5° C. and the solid collected by filtration to give 6-amino-3-methyl-1-(2-methyl-allyl)-1H-pyrimidine-2,4dione, mp 162-163° C. The methyluracil (165 g, 0.85 mol) is suspended in water (1.55 l) and concentrated hydrochloric acid (72 ml). A solution of sodium nitrite (58.4 g, 0.85 mol) in water (117 ml) is then added dropwise over 30 minutes and the reaction is stirred at 20° C. for 3 hours. The solid is collected by filtration, washed successively with water, methanol and ether to afford 6-amino-3-methyl-1-(2-methyl-allyl)-5-nitroso-1H-pyrimidine-2,4dione, mp 213° C. (dec). The nitrosouracil (190 g, 0.85 mol) is suspended in water (950 ml), heated to 85° C. and sodium dithionite (85%, 347.2 g, 1.69 mol) is added portionwise. After cooling to room temperature, the solid is collected by filtration to afford 5,6-diamino-3-methyl-1-(2-methyl-allyl)-1H-pyrimidine2,4-dione, mp 152-153° C.

Workup

  1. temperaturecooled to 0° C.
  2. filtrationThe resultant solid is collected by filtration
  3. washwashed with ether
  4. temperatureheated to 75° C
  5. addition2M aqueous sodium hydroxide solution is then added portionwise over 30 min
  6. temperatureto maintain pH between 8 and 9.5
  7. temperatureThe reaction is cooled to room temperature
  8. additiontreated with acetic acid (12 ml)
  9. temperaturefurther cooled to 10° C.
  10. filtrationthe resultant solid is collected by filtration
  11. washwashed with cold water
  12. customdried

Sources & evidence

ORD record
ord-4e141cef6f3b4566a236c60c0491ff57
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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