2,6-Di-tert-butyl-4-methylphenol → 2,4-Diamino-6-methyl-5-[3-(4-fluorophenyl)-3-methyl-1-butenyl]pyrimidine

HRID 54260

반응식

HRID 54260 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:25])([CH3:24])[CH:9]=[CH:10][Sn](CCCC)(CCCC)CCCC)=[CH:4][CH:3]=1.[NH2:26][C:27]1[N:32]=[C:31]([NH2:33])[C:30](I)=[C:29]([CH3:35])[N:28]=1.[Cl-].[Li+].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:26][C:27]1[N:32]=[C:31]([NH2:33])[C:30]([CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)([CH3:24])[CH3:25])=[C:29]([CH3:35])[N:28]=1

참가 물질

8

반응물 4

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 433294Lithium ChlorideHCID 158557925-Iodo-6-methylpyrimidine-2,4-diamineHCID 676315243-(4-Fluorophenyl)-3-methyl-1-tributylstannyl-1-butene

생성물 1

HCID 545098222,4-Diamino-6-methyl-5-[3-(4-fluorophenyl)-3-methyl-1-butenyl]pyrimidine수율 23.3%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

Under a nitrogen atmosphere, a stirring solution of 4.2 grams (0.009 mole) of 3-(4-fluorophenyl)-3-methyl-1-tributylstannyl-1-butene, 1.9 grams (0.077 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3), 2.0 grams (0.046 mole) of lithium chloride, 0.4 gram (catalyst) of bis(triphenyl phosphine)palladium(II) chloride, and about 0.05 gram (catalyst) of 2,6-di-tert-butyl-4-methylphenol in 80 mL of N,N-dimethylformamide is heated at 65° C. for about 2.5 days. After this time the reaction mixture is cooled and poured into 500 mL of water. The mixture then is extracted with three 100 mL portions of ethyl acetate. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is subjected to column chromatography on basic alumina (containing 6% water), using 10% methanol in methylene chloride as the eluant. The product-containing fractions are combined and concentrated under reduced pressure to a residue. NMR analysis of the residue indicates an impure product. The residue is subjected to column chromatography on silica gel, using 10% methanol in methylene chloride as the eluant. The product-containing fractions are combined and concentrated under reduced pressure, yielding about 0.6 gram of 2,4-diamino-6-methyl-5-[3-(4-fluorophenyl)-3-methyl-1-butenyl]pyrimidine, mp 164°-168° C. (Compound 66). The NMR spectrum is consistent with the proposed structure.

후처리

  1. temperatureAfter this time the reaction mixture is cooled
  2. extractionThe mixture then is extracted with three 100 mL portions of ethyl acetate
  3. dry with materialThe combined extracts are dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate is concentrated under reduced pressure to a residue
  6. concentrationconcentrated under reduced pressure to a residue
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-0af48c59a66d449c927f692a40730ac6
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05622954

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