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 1434986노트

반응식

HRID 1434986 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 86610959THF isopentane용매

실험 절차

[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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-e853bfed3e8c4a1885d0b81aff153309
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07615562B2

반응 노트

불러오는 중…