Diisopropylethylamine → 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972592노트

반응식

HRID 1972592 반응식
[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][NH:15][C@@H:14]([CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[CH2:13]2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].ClC1N=[CH:31][C:30]([C:33]([OH:42])([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35])=[CH:29]N=1.CCN(C(C)C)[CH:46]([CH3:48])[CH3:47]>O1CCOCC1>[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:46]3[CH:48]=[CH:31][C:30]([C:33]([OH:42])([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35])=[CH:29][CH:47]=3)[C@@H:14]([CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[CH2:13]2)(=[O:10])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 66582427(3S)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-methylmorpholineHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2회

생성물 1

HCID 866704002-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol수율 72.5%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A 20-mL vial was charged with (3S)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-methylmorpholine (0.797 g, 2.04 mmol, step 4), (2-chloro-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.859 g, 3.06 mmol, Intermediate D), DIPEA (1.10 mL, 6.30 mmol) and 1,4-dioxane (10 mL). The vial was sealed and heated at 100° C. for 12 h. The reaction mixture was allowed to cool to room temperature and then partitioned between water (30 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (40 mL). The combined organic phases were washed with saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes) to afford 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.936 g) as a tan solid.

후처리

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. custompartitioned between water (30 mL) and EtOAc (20 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (40 mL)
  5. washThe combined organic phases were washed with saturated aqueous NaCl (50 mL)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-ce385dbe78764811b12037597b86b4c7
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431563B2

반응 노트

불러오는 중…