Sodium ethoxide → 6-Amino-5-(2,2-diethoxyethyl)pyrimidin-4-ol

HRID 397374Notes

Reaction equation

HRID 397374 reaction equation
[O-]CC.[Na+].Cl.[CH:6]([NH2:8])=[NH:7].C(O[C:12](=[O:24])[CH:13]([C:22]#[N:23])[CH2:14][CH:15]([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])C>C(O)C>[NH2:23][C:22]1[N:7]=[CH:6][NH:8][C:12](=[O:24])[C:13]=1[CH2:14][CH:15]([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 4151505Ethyl 2-cyano-4,4-diethoxybutyrateHCID 10313058Methanimidamide, hydrochloride (1:1)

Product 1

HCID 1354086886-Amino-5-(2,2-diethoxyethyl)pyrimidin-4-olYield 66%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 45.2 mmol of sodium ethoxide (made in situ from sodium and absolute ethanol) in 40 mL of absolute ethanol was added formamidine hydrochloride (1.74 g, 21.5 mmol) and 2-cyano-4,4-diethoxy-butyric acid ethyl ester (2.47 g, 11 mmol, literature reference: Davoll, J., J. Chem. Soc. 131-138 (1960)). The mixture was refluxed for 6 hours, cooled to room temperature and filtered. The solid was washed with hot acetonitrile. The filtrate was neutralized with acetic acid to pH 6.5 and then evaporated to half of the volume. Ethyl acetate (50 mL) was added to the resultant filtrate. The precipitate was filtered, washed with EtOAc to give 1.6 g (66%) of 6-amino-5-(2,2-diethoxy-ethyl)-3H-pyrimidin-4-one as a white solid which was used without further purification. 1H NMR (300 MHz, DMSO-d6) δ 11.46 (s, br, 1H, NH), 7.68 (s, 1H), 6.07 (s, br, 2H, NH2), 4.54 (t, J=6.0 Hz, 1H, CH(OCH2CH3)2), 3.53-5.62 (m, 2H, CH(OCH2CH3)2), 3.31-3.49 (m, 2H, CH(OCH2CH3)2), 2.50 (m, 2H, CH2), and 1.05 (t, J=6.93 Hz, 6H, CH(OCH2CH3)2).

Workup

  1. temperatureThe mixture was refluxed for 6 hours
  2. filtrationfiltered
  3. washThe solid was washed with hot acetonitrile
  4. customevaporated to half of the volume
  5. additionEthyl acetate (50 mL) was added to the resultant filtrate
  6. filtrationThe precipitate was filtered
  7. washwashed with EtOAc

Sources & evidence

ORD record
ord-6e0bc1bf18eb43208ccb020099b92b22
Source dataset
uspto-grants-2003_08
Patent number
US06610688B2

Reaction notes

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