Iodine → [4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl](2-thienyl)methanone

HRID 2082031Notes

Reaction equation

HRID 2082031 reaction equation
[Mg].II.Br[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[Br-].[Mg+2].S1C=CC=C1.[Br-].[CH3:18][C:19]([C:22]1[C:27]([OH:28])=[C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])[N:25]=[C:24]([C:33](N(OC)C)=[O:34])[N:23]=1)([CH3:21])[CH3:20]>C(OCC)C.O1CCCC1.C(O)(C)C>[CH3:21][C:19]([C:22]1[C:27]([OH:28])=[C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])[N:25]=[C:24]([C:33]([C:5]2[S:6][CH:7]=[CH:8][CH:9]=2)=[O:34])[N:23]=1)([CH3:18])[CH3:20]

Participants

9

Reactant 5

HCID 807IodineHCID 138512-BromothiopheneHCID 5462224MagnesiumHCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideHCID 68448211Thiophene magnesium bromide

Product 1

HCID 10245342[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl](2-thienyl)methanoneYield 74%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent3×HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of magnesium turnings (1.22 g, 50.7 mmol) in dry ethyl ether (16 mL) under nitrogen atmosphere is added a single crystal of iodine followed by freshly distilled 2-bromothiophene (2.50 mL, 30.0 mmol) dropwise over 1 hour. This mixture is refluxed 1 hour then cooled to room temperature. The molarity of the solution (1.06M) is determined by titration of a small sample with isopropanol. A portion of this 1.06M solution of thiophene magnesium bromide in ether (3.5 mL, 3.71 mmol) is added dropwise under nitrogen atmosphere to a solution of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide (0.50 g, 1.7 mmol) in tetrahydrofuran (15 mL) dropwise. The resulting mixture is stirred 16 hours, diluted with ethyl ether (15 mL), quenched with aqueous saturated ammonium chloride solution, and washed with water and brine solution. Concentration of the organic phase followed by purification by flash chromatography (SiO2, dichloromethane) and recrystallization from methanol and water gave 0.40 g (74 %) of title compound, mp 157.5°-159° C.

Workup

  1. temperatureThis mixture is refluxed 1 hour
  2. customquenched with aqueous saturated ammonium chloride solution
  3. washwashed with water and brine solution
  4. customConcentration of the organic phase followed by purification by flash chromatography (SiO2, dichloromethane) and recrystallization from methanol and water

Sources & evidence

ORD record
ord-ac08b084ae054751997961fdcc96ff71
Source dataset
uspto-grants-1993_02
Patent number
US05187175

Reaction notes

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