Diisopropylethylamine → Ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate

HRID 1798908Notes

Reaction equation

HRID 1798908 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([Cl:13])[N:5]=[C:4]([S:14][CH3:15])[N:3]=1.[CH3:16][O:17][C:18]1[CH:33]=[CH:32][C:21]([CH2:22][NH:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:13][C:6]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([N:23]([CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:22][C:21]2[CH:20]=[CH:19][C:18]([O:17][CH3:16])=[CH:33][CH:32]=2)[N:3]=[C:4]([S:14][CH3:15])[N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 533817Ethyl 4,6-dichloro-2-(methylsulfanyl)pyrimidine-5-carboxylateHCID 59506403Ethyl 4-((4-methoxybenzyl)amino)butanoate

Product 1

HCID 59506504Ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylateYield 57.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of ethyl 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylate (7.9 g, 29.88 mmol) and ethyl 4-((4-methoxybenzyl)amino)butanoate (5 g, 19.92 mmol) in DMF (500 mL) and DIPEA (4.6 g, 35.85 mmol) was heated at 80° C. for 2 h. The reaction mixture was then cooled to room temperature and crushed ice was added. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined EtOAc layer was dried over sodium sulphate, filtered and evaporated under reduced pressure to give a residue which was purified by column chromatography (silica gel, gradient 0-5% EtOAc in hexanes) to afford ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (5.5 g, 40%). 1H NMR (400 MHz, CDCl3): δ 7.12 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 4.66 (s, 2H), 4.16 (q, J=6.8 Hz, 2H), 4.10 (q, J=7.2 Hz, 2H), 3.79 (s, 3H), 3.42 (t, J=7.6 Hz, 2H), 2.45 (s, 3H), 2.24 (t, J=6.8 Hz, 2H), 1.94 (quintet, J=7.2 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H). LCMS [M+H]: 482

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customcrushed ice
  3. additionwas added
  4. extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
  5. dry with materialthe combined EtOAc layer was dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give a residue which
  9. customwas purified by column chromatography (silica gel, gradient 0-5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7dac9f0231344a86aefeae8db62305e6
Source dataset
uspto-grants-2013_01
Patent number
US08343983B2

Reaction notes

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