Ammonium Chloride → ((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(pyrimidin-2-yl)methanol

HRID 1876924노트

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HRID 1876924 반응식
C([Sn](CCCC)(CCCC)[C:6]1[N:11]=[CH:10][CH:9]=[CH:8][N:7]=1)CCC.C([Li])CCC.[Br-].[Mg+2].[Br-].[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:36]=[CH:37][N:38]3[C:47]=2[CH:46]=[C:45]2[C@@:40]([CH3:50])([C@@H:41]([CH:48]=[O:49])[CH2:42][CH2:43][CH2:44]2)[CH2:39]3)=[CH:31][CH:30]=1.[Cl-].[NH4+]>C1COCC1>[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:36]=[CH:37][N:38]3[C:47]=2[CH:46]=[C:45]2[C@@:40]([CH3:50])([C@@H:41]([CH:48]([C:6]4[N:7]=[CH:8][CH:9]=[CH:10][N:11]=4)[OH:49])[CH2:42][CH2:43][CH2:44]2)[CH2:39]3)=[CH:31][CH:30]=1

참가 물질

7

반응물 5

HCID 25517Ammonium ChlorideHCID 82241Magnesium BromideHCID 27632512-(Tributylstannyl)pyrimidineHCID 46180541(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehydeHCID 178418339Butyllithium

생성물 1

HCID 67445673((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(pyrimidin-2-yl)methanol

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

To a stirred solution of 2-(tributylstannyl)pyrimidine (185 mg, 0.5 mmol) in anhydrous THF (1 mL) was added butyllithium solution (1.6 M in hexanes, 0.31 mL, 0.5 mmol) dropwise at −78° C. under nitrogen. The mixture was stirred at −78° C. for 2 hr before magnesium bromide (90 mg, 0.5 mmol) was added. After the reaction mixture was stirred at −78° C. for additional 30 min, (5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehyde (Example 1g, 20 mg, 0.065 mmol) was added. The mixture was stirred at −78° C. for 45 min and at RT for 5 min. Saturated aqueous ammonium chloride solution (2 mL) was added. The reaction mixture was extracted with ethyl acetate (3×1 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (50-100% ethyl acetate in heptanes and then 0-20% methanol in ethyl acetate) gave ((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(pyrimidin-2-yl)methanol which was used as such for the subsequent step without further purification.

후처리

  1. additionwas added
  2. stirringThe mixture was stirred at −78° C. for 45 min and at RT for 5 min
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×1 mL)
  4. dry with materialThe combined organic solutions were dried (Na2SO4)
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-b471998a285c4e16aba9a205a1a76797
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309730B2

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