Ethylamine → Ethyl 4-(ethylamino)-2-(methylthio)pyrimidine-5-carboxylate

HRID 1793877Notes

Reaction equation

HRID 1793877 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.[CH2:15]([N:17](CC)CC)[CH3:16].O1CCCC1.C(N)C>C(OCC)(=O)C.CCCCCCC>[CH2:11]([O:10][C:8]([C:7]1[C:2]([NH:17][CH2:15][CH3:16])=[N:3][C:4]([S:13][CH3:14])=[N:5][CH:6]=1)=[O:9])[CH3:12]

Participants

7

Reactant 4

HCID 6341EthylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester

Product 1

HCID 10514260Ethyl 4-(ethylamino)-2-(methylthio)pyrimidine-5-carboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

A 22-L, 4-necked round-bottomed flask was equipped with a mechanical stirrer, a dropping funnel, and a thermometer. The flask was charged with the ethyl 4-chloro-2-(methylthio)-5-pyrimidinecarboxylate (1.53 kg, 6.56 mol), triethylamine (2.74 L, 19.7 mol, 3 eq), and 7.5 L of tetrahydrofuran to give a solution. The aqueous ethylamine (0.53 L, 6.56 mol, 1 eq) was added via the dropping funnel over 20 minutes. The reaction temperature rose to 35° C. during the addition. The reaction was stirred at ambient temperature for 2 hours. The reaction was checked for completion using TLC (SiO2; 7:3/heptane:ethyl acetate). The precipitate (triethylamine hydrochloride) was filtered off and washed 2 times with tetrahydrofuran, combining the washes with the original filtrate. The tetrahydrofuran was stripped to near dryness on a rotary evaporator. The residue was partitioned between saturated aqueous sodium bicarbonate (500 mL) and ethyl acetate (1 L). Note that there is carbon dioxide gas evolution from the bicarbonate both during the partitioning and the subsequent washes. The layers were separated and the organic layer washed 2 times with saturated aqueous sodium bicarbonate and 1 time with brine. The solution was dried over magnesium sulfate, filtered, and stripped to give the titled compound as an off-white solid. Yield: 95%.

Workup

  1. customto give a solution
  2. additionThe reaction temperature rose to 35° C. during the addition
  3. filtrationThe precipitate (triethylamine hydrochloride) was filtered off
  4. washwashed 2 times with tetrahydrofuran
  5. customon a rotary evaporator
  6. customThe residue was partitioned between saturated aqueous sodium bicarbonate (500 mL) and ethyl acetate (1 L)
  7. customThe layers were separated
  8. washthe organic layer washed 2 times with saturated aqueous sodium bicarbonate and 1 time with brine
  9. dry with materialThe solution was dried over magnesium sulfate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-b6f807721d8447d7a14b0993afbc146a
Source dataset
uspto-grants-2006_04
Patent number
US07022711B2

Reaction notes

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