Triethylamine → (R)-2-methylsulfanyl-4-(tetrahydrofuran-3-ylamino)-pyrimidine-5-carboxylic acid ethyl ester

HRID 1243173Notes

Reaction equation

HRID 1243173 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.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:33][C@@H:34]1[CH2:38][CH2:37][O:36][CH2:35]1>O1CCOCC1>[CH2:11]([O:10][C:8]([C:7]1[C:2]([NH:33][C@@H:34]2[CH2:38][CH2:37][O:36][CH2:35]2)=[N:3][C:4]([S:13][CH3:14])=[N:5][CH:6]=1)=[O:9])[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 142431694-Methylbenzene-1-sulfonic acid--(3R)-oxolan-3-amine (1/1)

Product 1

HCID 11150267(R)-2-methylsulfanyl-4-(tetrahydrofuran-3-ylamino)-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (897 mg, 3.86 mmol) (Aldrich) and triethylamine (1.2 mL, 870 mg, 8.49 mmol) (Aldrich) in dioxane (20 mL) was treated with (R)-3-aminotetrahydrofuran p-toluene-sulfonic acid salt (1.0 g, 3.86 mmol) (Fluka). The mixture was stirred at reflux for 1 hour, then cooled and partitioned between brine and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, concentrated and the residue was purified by chromatography with a silica gel column using a 0–100% ethyl acetate in hexanes gradient to give (R)-2-methylsulfanyl-4-(tetrahydrofuran-3-ylamino)-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 1.0 g, 92%).

Workup

  1. temperatureat reflux for 1 hour
  2. temperaturecooled
  3. custompartitioned between brine and ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by chromatography with a silica gel column

Sources & evidence

ORD record
ord-cb68d6f41f2d4a38bcfa649137dc64df
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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