4,6-Dichloro-5-nitropyrimidine → [4-(6-Chloro-5-nitro-pyrimidin-4-ylamino)-phenyl]-acetic acid ethyl ester

HRID 1661037Notes

Reaction equation

HRID 1661037 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1)[CH3:2].[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19](Cl)[N:18]=[CH:17][N:16]=1>>[CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:19]2[C:20]([N+:21]([O-:23])=[O:22])=[C:15]([Cl:14])[N:16]=[CH:17][N:18]=2)=[CH:10][CH:11]=1)[CH3:2]

Participants

3

Reactant 2

HCID 203124,6-Dichloro-5-nitropyrimidineHCID 225219p-Aminophenylacetic acid ethyl ester2×

Product 1

HCID 86625829[4-(6-Chloro-5-nitro-pyrimidin-4-ylamino)-phenyl]-acetic acid ethyl ester

Procedure

4-Aminophenylacetic acid ethyl ester (0.93 g, 5.2 mmol) is added to a solution of 4,6-dichloro-5-nitropyrimidine (2 g, 10.4 mmol, 2 equiv). The resulting mixture is stirred for 2 h at rt and 4-aminophenylacetic acid ethyl ester (0.47 g, 2.6 mmol, 0.5 equiv) is added. The reaction mixture is stirred for 15 min and filtered. The filtrate is concentrated. The residue is dissolved in EtOAc and a saturated aqueous solution of sodium bicarbonate. The layers are separated. The aqueous phase is extracted with EtOAc. The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the residue by silica gel column chromatography (Hexane/EtOAc, 4:1) provides the title compound as a yellow solid: ES-MS: 335.0/337.0 [M-H]−; single peak at tR=4.73 min (System 1); Rf=0.22 (Hexane/EtOAc, 4:1).

Workup

  1. stirringThe reaction mixture is stirred for 15 min
  2. filtrationfiltered
  3. concentrationThe filtrate is concentrated
  4. dissolutionThe residue is dissolved in EtOAc
  5. customThe layers are separated
  6. extractionThe aqueous phase is extracted with EtOAc
  7. washThe combined organic phase is washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the residue by silica gel column chromatography (Hexane/EtOAc, 4:1)

Sources & evidence

ORD record
ord-9619c52c8b8f4f2a8565a91009a82ccd
Source dataset
uspto-grants-2011_10
Patent number
US08030311B2

Reaction notes

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