1-(3-Nitrobenzyl)urea → 6-Amino-1-(3-amino-benzyl)-3-methyl-1h-pyrimidine-2,4-dione acetic acid salt

HRID 900699Notes

Reaction equation

HRID 900699 reaction equation
[N+](C1C=C(C=CC=1)CNC(N)=O)([O-])=[O:2].[NH2:15][C:16]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-])=O)[CH:24]=2)[C:20](=[O:32])[N:19]([CH3:33])[C:18](=[O:34])[CH:17]=1>C(O)C.[Pd]>[C:18]([OH:34])(=[O:2])[CH3:17].[NH2:15][C:16]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([NH2:29])[CH:24]=2)[C:20](=[O:32])[N:19]([CH3:33])[C:18](=[O:34])[CH:17]=1

Participants

5

Reactant 2

HCID 106554621-(3-Nitrobenzyl)ureaHCID 222264816-amino-3-methyl-1-(3-nitro-benzyl)-1H-pyrimidine-2,4-dione

Product 1

HCID 222265016-Amino-1-(3-amino-benzyl)-3-methyl-1h-pyrimidine-2,4-dione acetic acid salt

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Using the general procedure for Intermediate 1, (3-nitrobenzyl)-urea [J. Med. Chem. 1996, 39, 1924] is converted into 6-amino-3-methyl-1-(3-nitro-benzyl)-1H-pyrimidine-2,4-dione, [M-H]− 275. A suspension of this compound (4.88 g, 17.7 mmol) and 10% Pd/C (0.484 g) in ethanol (200 ml) is hydrogenated at 1 atmosphere for 1.5 hours. The reaction mixture is filtered through a celite plug and evaporated to give 6-amino-1-(3-amino-benzyl)-3-methyl-1H-pyrimidine-2,4-dione acetic acid salt [M-H]− 245. Acetic anhydride (1.85 ml, 19.57 mmol) is added to a cooled (0° C.) suspension of 6-amino-1-(3-amino-beryl)-3-methyl-1H-pyrimidine-2,4-dione acetic acid salt (5.01 g, 16.35 mmol) in pyridine (50 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-[3-(6-amino-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-phenyl]-acetamide, 1H NMR (400 MHz, DMSO): δ: 2.00 (s 3H), 3.09 (s 3H), 4.72 (s 1H), 5.02 (s 2H), 6.75 (s 2H), 6.88 (d J 6 1H), 7.25 (t J 6 1H), 7.30 (s 1H), 7.55 (d J 6 1H). Using the general procedure for Intermediate 1, this compound is converted into N-[3-(5,6-diamino-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-phenyl]-acetamide [MH]+ 304.

Workup

  1. filtrationThe reaction mixture is filtered through a celite plug
  2. customevaporated

Sources & evidence

ORD record
ord-0542008d805741b1b6a5b6ff46e0215f
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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