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

HRID 2082031노트

반응식

HRID 2082031 반응식
[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]

참가 물질

9

반응물 5

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

생성물 1

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

시약·촉매·용매 3

HCID 3283Diethyl Ether용매3회HCID 3776Isopropanol용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ac08b084ae054751997961fdcc96ff71
출처 데이터셋
uspto-grants-1993_02
특허 번호
US05187175

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