Calcium Chloride → HCID 22226572, compound

HRID 900700Notes

Reaction equation

HRID 900700 reaction equation
[N+](C1C=CC(CNC(N)=O)=CC=1)([O-])=[O:2].[NH2:15][C:16]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][CH:24]=2)[C:20](=[O:32])[N:19]([CH3:33])[C:18](=[O:34])[CH:17]=1.[Cl-].[Ca+2].[Cl-]>O.C(O)(=O)C.[Zn]>[C:18]([OH:34])(=[O:2])[CH3:17].[NH2:15][C:16]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=2)[C:20](=[O:32])[N:19]([CH3:33])[C:18](=[O:34])[CH:17]=1

Participants

7

Reactant 3

HCID 5284359Calcium ChlorideHCID 1490607918740-35-7HCID 22226533HCID 22226533, compound2×

Product 1

HCID 22226572HCID 22226572, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

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. filtrationfiltered through a celite plug
  2. washwashed successively with ethanol and acetic acid
  3. customEvaporation of the combined filtrate and washings

Sources & evidence

ORD record
ord-51ffeecb0098438a9a15054dbd9751f2
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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