Tetrahydrofuran → 3-(4-Ethylamino-2-phenylamino-pyrimidin-5-yl)-but-2-enoic acid ethyl ester

HRID 2300069Notes

Reaction equation

HRID 2300069 reaction equation
[CH2:1]([NH:3][C:4]1[C:9]([CH:10]=O)=[CH:8][N:7]=[C:6]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:5]=1)[CH3:2].[C:19]([CH2:24]C=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:21][CH2:22][CH3:23])=[O:20].O1CCC[CH2:46]1>>[CH2:22]([O:21][C:19](=[O:20])[CH:24]=[C:10]([C:9]1[C:4]([NH:3][CH2:1][CH3:2])=[N:5][C:6]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:7][CH:8]=1)[CH3:46])[CH3:23]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 108240804-Ethylamino-2-phenylamino-pyrimidine-5-carbaldehydeHCID 12607919Ethyl 3-(triphenyl-lambda~5~-phosphanylidene)propanoate

Product 1

HCID 543804503-(4-Ethylamino-2-phenylamino-pyrimidin-5-yl)-but-2-enoic acid ethyl esterYield 65%

Procedure

To a room temperature solution of 4-ethylamino-2-phenylamino-pyrimidine-5-carboxaldehyde (200 mg, 0.83 mmol) in 10 mL of tetrahydrofuran was added (carbethoxyethylidene)triphenylphosphorane (360 mg, 1.0 mmol). The reaction mixture was heated at reflux overnight, cooled, and concentrated in vacuo. The residue was purified by flash chromatography eluting with 1:1 ethyl acetate:hexane. The fractions containing product were concentrated, and 1:2 ethyl acetate:hexane was added to the residue. The resultant solid was collected by filtration to provide 176 mg (65%) of 3-(4-ethylamino-2-phenylamino-pyrimidin-5-yl)-but-2-enoic acid ethyl ester, mp 148-150° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. temperaturecooled
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. washeluting with 1:1 ethyl acetate
  7. additionThe fractions containing product
  8. concentrationwere concentrated
  9. addition1:2 ethyl acetate:hexane was added to the residue
  10. filtrationThe resultant solid was collected by filtration

Sources & evidence

ORD record
ord-bcf7b512d386446d915b231ebdde365f
Source dataset
uspto-grants-2002_12
Patent number
US06498163B1

Reaction notes

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