Acetic Anhydride → HCID 22226558, compound

HRID 1745801Notes

Reaction equation

HRID 1745801 reaction equation
C(O[C:5](=[O:7])[CH3:6])(=O)C.C(O)(=O)C.[NH2:12][C:13]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)[C:17](=[O:27])[N:16]([CH3:28])[C:15](=[O:29])[CH:14]=1>N1C=CC=CC=1>[NH2:12][C:13]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:5](=[O:7])[CH3:6])=[CH:22][CH:21]=2)[C:17](=[O:27])[N:16]([CH3:28])[C:15](=[O:29])[CH:14]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 22226572HCID 22226572, compound

Product 1

HCID 22226558HCID 22226558, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Using the general procedure for Intermediate 1, (4-nitro-benzyl)-urea [J. Med. Chem. 1996, 39, 1924] is converted into 6-amino-3-methyl-1-(4-nitro-benzyl)-1H-pyrimidine-2,4-dione, [MH]+ 277. A solution of calcium chloride (4.94 g, 45 mmol) in water (100 ml) is added to a solution of 6-amino-3-methyl-1-(4-nitro-benzyl)-1H-pyrimidine-2,4-dione (19.08 g, 69.0 mmol) in acetic acid (300 ml). Zinc dust (58.8 g, 900 mmol) is then added portionwise with external cooling. The reaction is stirred at room temperature for 1.5 hours, filtered through a celite plug and washed successively with ethanol and acetic acid. Evaporation of the combined filtrate and washings affords 6-amino-1-(4-amino-benzyl)-3-methyl-1H-pyrimidine-2,4-dione acetic acid salt, [M−3H]− 243. Acetic anhydride (7.2 ml, 76.0 mmol) is added to a cooled (0° C.) suspension of 6-amino-1-(4-amino-benzyl)-3-methyl-1H-pyrimidine-2,4-dione acetic acid salt (17.0 g, 69.0 mmol) in pyridine (260 ml). The reaction mixture is warmed to room temperature, stirred for 6 hours and the solvent evaporated. The residue is triturated with water and the solid collected by filtration and dried to afford N-[4-(6-amino-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-phenyl]-acetamide, [MH]+ 289. Using the general procedure for Intermediate 1, this compound is converted into N-[4-(5,6-diamino-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-phenyl]-acetamide, [MH]+ 304.

Workup

  1. temperaturea cooled
  2. customthe solvent evaporated
  3. customThe residue is triturated with water
  4. filtrationthe solid collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-f31a4c9166814de69f2fcd15b2f15fc1
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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