Carbamimidic acid, methyl ester, sulfate (1:1) → 4-(2-Azido-ethoxymethyl)-6-(2-chloro-phenyl)-2-methoxy-1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester

HRID 1374685Notes

Reaction equation

HRID 1374685 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]([C:14](=O)[CH2:15][O:16][CH2:17][CH2:18][N:19]=[N+:20]=[N-:21])=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13])[CH3:2].S(O)(O)(=O)=O.[CH3:29][O:30][C:31](=[NH:33])[NH2:32].C(=O)(O)[O-].[Na+]>CN(C)C(=O)C.CCOC(C)=O.O>[CH2:1]([O:3][C:4]([C:5]1[CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:13])[NH:33][C:31]([O:30][CH3:29])=[N:32][C:14]=1[CH2:15][O:16][CH2:17][CH2:18][N:19]=[N+:20]=[N-:21])=[O:23])[CH3:2]

Participants

7

Reactant 3

HCID 169039Carbamimidic acid, methyl ester, sulfate (1:1)HCID 516892Sodium BicarbonateHCID 71433737Ethyl (2-Azidoethoxy)aceto-2-(2-chlorophenylmethlene)acetate

Product 1

HCID 1784693224-(2-Azido-ethoxymethyl)-6-(2-chloro-phenyl)-2-methoxy-1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-[2-(2-azido-ethoxy)-acetyl]-3-(2-chloro-phenyl)-acrylic acid ethyl ester (1.50 g, 4.44 mmol), O-methylisourea sulfate (0.82 g, 6.66 mmol) and sodium bicarbonate (1.5 g, 17.86 mmol) in N,N-dimethylacetamide (25 mL) was heated to 80° C. and maintained at this temperature overnight (ca. 15 h). The mixture was cooled to RT and then taken up in EtOAc (100 mL) and H2O (50 mL). The EtOAc extract was washed with brine (50 mL), dried (Na2SO4), filtered, concentrated and dried in vacuo. The crude product was purified by chromatography using the ISCO Combiflash SQ16× (120 g Redisep silica gel column, 0 to 60% EtOAc in hexanes for 30 min at 40 mL/min) to afford 1.189 g (68% for 2 steps) of white solid as a purified product.

Workup

  1. temperaturemaintained at this temperature overnight (ca. 15 h)
  2. temperatureThe mixture was cooled to RT
  3. extractionThe EtOAc extract
  4. washwas washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customdried in vacuo
  9. customThe crude product was purified by chromatography
  10. custom× (120 g Redisep silica gel column, 0 to 60% EtOAc in hexanes for 30 min at 40 mL/min) to afford 1.189 g (68% for 2 steps) of white solid as a purified product

Sources & evidence

ORD record
ord-03754c4907c54f78906b5bdeaf63142d
Source dataset
uspto-grants-2007_01
Patent number
US07166603B2

Reaction notes

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