1-Methyl-4-piperidone → 1-Methyl-4-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-piperidin-4-ol

HRID 1434986ノート

反応式

HRID 1434986 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]3[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]3)[N:9]=2)=[CH:4][CH:3]=1.[Li]CCCC.[CH3:30][N:31]1[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]1>C1COCC1.CCC(C)C.C1COCC1>[CH3:30][N:31]1[CH2:36][CH2:35][C:34]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]4[CH2:16][C:17]([CH3:24])([CH3:23])[NH:18][C:19]([CH3:22])([CH3:21])[CH2:20]4)[N:9]=3)=[CH:6][CH:7]=2)([OH:37])[CH2:33][CH2:32]1

参加物

6

反応物 3

HCID 740491-Methyl-4-piperidoneHCID 57936126[4-(4-Bromophenyl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amineHCID 178418339Butyllithium

生成物 1

HCID 579362251-Methyl-4-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-piperidin-4-ol

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 86610959THF isopentane溶媒

実験手順

[4-(4-Bromophenyl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (116 mg; 0.3 mmol) in THF/isopentane (3 ml/0.6 ml) was cooled to −100° C. nBuLi (1.6M in hexane, 0.56 ml; 0.9 mmol) was added within 5 minutes and the reaction mixture stirred for 15 minutes at this temperature. N-methyl-4-piperidone (71 μl, 0.6 mmol) was added in THF (71 μl), the reaction mixture stirred for 10 minutes at −100° C., poured on water and extracted three times with EtOAc. The combined organic phases were dried over sodium sulfate, filtered, evaporated to dryness and purified via chromatography on silicagel (EtOAc/MeOH/ammonia:90/9/1 to 80/18/2) to give the title compound as a white solid. Yield: 25 mg (17%).

後処理

  1. additionwas added within 5 minutes
  2. stirringthe reaction mixture stirred for 10 minutes at −100° C.
  3. additionpoured on water
  4. extractionextracted three times with EtOAc
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. custompurified via chromatography on silicagel (EtOAc/MeOH/ammonia:90/9/1 to 80/18/2)

出典と根拠

ORDレコード
ord-e853bfed3e8c4a1885d0b81aff153309
出典データセット
uspto-grants-2009_11
特許番号
US07615562B2

反応ノート

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