Methane → 2-Amino-alpha-cyano-1, 6-dihydro-5-nitro-6-oxo-alpha-(2-thienylmethyl)-4-pyrimidine-acetic acid, methyl ester

HRID 1029384Notes

Reaction equation

HRID 1029384 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:23])[C:5]([N+:20]([O-:22])=[O:21])=[C:6]([C:8]([C:18]#[N:19])([CH2:12][C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:9]([OH:11])=[O:10])[N:7]=1.C.N[C:26]1NC(=O)C([N+]([O-])=O)=C(Cl)N=1.Cl>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[NH:3][C:4](=[O:23])[C:5]([N+:20]([O-:22])=[O:21])=[C:6]([C:8]([C:18]#[N:19])([CH2:12][C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:9]([O:11][CH3:26])=[O:10])[N:7]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 313Hydrochloric AcidHCID 1354086932-Amino-6-chloro-5-nitro-3,4-dihydropyrimidin-4-oneHCID 1360252442-Amino-alpha-cyano-1,6-dihydro-5-nitro-6-oxo-alpha-(2-thienylmethyl)-4-pyrimidineacetic acid

Product 1

HCID 1364033682-Amino-alpha-cyano-1, 6-dihydro-5-nitro-6-oxo-alpha-(2-thienylmethyl)-4-pyrimidine-acetic acid, methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

2-Amino-α-cyano-1,6-dihydro-5-nitro-6-oxo-α-(2-thienylmethyl)-4-pyrimidineacetic acid, methyl hydride (4.5 g, 60% suspension in oil washed with hexane) is suspended in dry DMF (50 mL) under an atmosphere of dry N2 and a solution of methyl 2-cyano- 3-(2-thienyl) propionate (U.S. Pat. No. 4,279,903) (22.0 g) in dry DMF (50 mL) is added dropwise when a dark blue solution is formed. A solution of freshly recrystallized 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone (8.57 g) in DMF (75 mL) is added in one portion. The reaction mixture is heated at 60° C. overnight and cooled and then is acidified to pH 5 with 1N HCl. It is poured into 1000 mL ethyl acetate and is extracted with water (4×300 mL). The organic layer is evaporated to near dryness and the residue is suspended in ether and collected by filtration. The crude product is washed with hexane until the washings are no longer green. The solid is dried under vacuum to give 2-Amino-α-cyano-1, 6-dihydro-5-nitro-6-oxo-α-(2-thienylmethyl)-4-pyrimidine-acetic acid, methyl ester. ##STR14##

Workup

  1. customis formed
  2. temperaturecooled
  3. extractionis extracted with water (4×300 mL)
  4. customThe organic layer is evaporated
  5. filtrationcollected by filtration
  6. washThe crude product is washed with hexane until the washings
  7. customThe solid is dried under vacuum

Sources & evidence

ORD record
ord-625eb3df3df747f2a9fa7299c2f5f129
Source dataset
uspto-grants-1992_04
Patent number
US05102879

Reaction notes

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