Hydrogen Bromide → 3-(3-Methyl-4-{5-[2-oxo-2-(4-trifluoromethylphenyl)ethyl]pyridin-2-yloxy}phenyl)-1-piperonyltetrahydropyrimidin-2-one hydrobromide

HRID 884179노트

반응식

HRID 884179 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]4[CH:30]=[CH:29][C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=4)[C:16]3=[O:31])=[CH:11][C:10]=2[CH3:32])=[N:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[F:75][C:76]([F:87])([F:86])[C:77]1[CH:82]=[CH:81][C:80]([C:83](=[O:85])[CH3:84])=[CH:79][CH:78]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[BrH:1].[CH3:32][C:10]1[CH:11]=[C:12]([N:15]2[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]3[CH:30]=[CH:29][C:28]4[O:27][CH2:26][O:25][C:24]=4[CH:23]=3)[C:16]2=[O:31])[CH:13]=[CH:14][C:9]=1[O:8][C:5]1[CH:4]=[CH:3][C:2]([CH2:84][C:83](=[O:85])[C:80]2[CH:79]=[CH:78][C:77]([C:76]([F:75])([F:86])[F:87])=[CH:82][CH:81]=2)=[CH:7][N:6]=1

참가 물질

9

반응물 5

HCID 260Hydrogen BromideHCID 697311-(4-(Trifluoromethyl)phenyl)ethan-1-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3251421Potassium bis(trimethylsilyl)amideHCID 685273963-[4-(5-Bromopyridin-2-yloxy)-3-methylphenyl]-1-piperonyltetrahydropyrimidin-2-one

생성물 1

HCID 685269463-(3-Methyl-4-{5-[2-oxo-2-(4-trifluoromethylphenyl)ethyl]pyridin-2-yloxy}phenyl)-1-piperonyltetrahydropyrimidin-2-one hydrobromide수율 33.2%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

To a solution of 3-[4-(5-bromopyridin-2-yloxy)-3-methylphenyl]-1-piperonyltetrahydropyrimidin-2-one (0.11 g, 0.22 mmol) in toluene (10 mL) were added Pd2(dba)3 (10 mg, 0.01 mmol) and Xantphos (15 mg, 0.03 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 5 minutes, and then 4′-(trifluoromethyl)acetophenone (63 mg, 0.33 mmol) and potassium bis(trimethylsilyl)amide (66 mg, 0.33 mmol) were added to the reaction % solution. The resulting solution was stirred at 70 to 80° C. for 30 minutes, and left to cool. Water was added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1), to yield 50 mg of a free form. To this free form was added an equivalent amount of hydrobromic acid, to thereby yield 50 mg of the title compound.

후처리

  1. stirringThe resulting solution was stirred at 70 to 80° C. for 30 minutes
  2. waitleft
  3. temperatureto cool
  4. extractionextracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  6. customevaporated
  7. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1)
  8. customto yield 50 mg of a free form

출처 및 근거

ORD 기록
ord-47e666046fbd40ab96f6f378cf31db05
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236826B2

반응 노트

불러오는 중…