Ammonium Chloride → 1-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}-2-methylpropan-2-ol

HRID 1042150ノート

反応式

HRID 1042150 の反応式
C(OC(=O)[CH2:5][CH:6]1[S:10][C:9]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([O:20][C:21]2[CH:22]=[N:23][C:24]([CH2:27][O:28][CH3:29])=[CH:25][CH:26]=2)=[CH:15][C:14]=3[O:30][CH:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[N:8][CH2:7]1)C.[O:38]1[CH2:42][CH2:41]CC1.[CH3:43][Mg]Br.[Cl-].[NH4+]>O1CCCC1.CCCCCC.C(OCC)(=O)C.CO>[CH3:29][O:28][CH2:27][C:24]1[N:23]=[CH:22][C:21]([O:20][C:16]2[CH:17]=[C:18]3[C:13](=[C:14]([O:30][CH:31]4[CH2:32][CH2:33][O:34][CH2:35][CH2:36]4)[CH:15]=2)[NH:12][C:11]([C:9]2[S:10][CH:6]([CH2:5][C:42]([CH3:41])([OH:38])[CH3:43])[CH2:7][N:8]=2)=[CH:19]3)=[CH:26][CH:25]=1

参加物

8

反応物 3

HCID 25517Ammonium ChlorideHCID 58081032ethyl{2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetateHCID 178420675HCID 178420675、化合物

生成物 1

HCID 580810681-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}-2-methylpropan-2-ol収率 15%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

実験手順

To a solution of ethyl{2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate (500 mg) in tetrahydrofuran (10 mL) was added 1M methylmagnesium bromide tetrahydrofuran solution (5 mL) twice at 30 min intervals at room temperature, and the mixture was stirred at room temperature for 3 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (ethyl acetate:hexane=0:100 to 100:0, volume ratio) and further to silica gel column chromatography (methanol:ethyl acetate:hexane=0:0:100 to 10:90:0, volume ratio). The obtained crude product was purified by preparative HPLC to give the title compound (75 mg, yield 15%) as white crystals.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customThe obtained crude product
  8. customwas purified by preparative HPLC

出典と根拠

ORDレコード
ord-af9cdbcb39314bbdb1c8a475e5c06085
出典データセット
uspto-grants-2013_10
特許番号
US08557805B2

反応ノート

読み込み中…