Diisopropylethylamine → 4-Amino-3-chloro-alpha-[[(phenylmethyl)[6-(2-pyridinylethoxy)hexyl]amino]methyl]-5-(trifluoromethyl)benzenemethanol

HRID 1032708노트

반응식

HRID 1032708 반응식
[NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12](=[O:15])[CH2:13]Br)=[CH:4][C:3]=1[Cl:16].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([CH:12]([CH2:13][N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][N:17]=2)[OH:15])=[CH:4][C:3]=1[Cl:16]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 133555211-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromo-ethanoneHCID 19876743N-[6-[2-(2-Pyridinyl)ethoxy]hexyl]benzenemethanamine

생성물 1

HCID 221649134-Amino-3-chloro-alpha-[[(phenylmethyl)[6-(2-pyridinylethoxy)hexyl]amino]methyl]-5-(trifluoromethyl)benzenemethanol수율 43.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

1-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromoethanone (2.1 g), N-[6-[2-(2-pyridinyl)ethoxy]hexyl]benzenemethanamine (2.20 g) and N,N-diisopropylethylamine (0.94 g) were stirred together in tetrahydrofuran (45 ml) for 24 h at room temperature under nitrogen. The mixture was filtered and the filtrate evaporated in vacuo. The residue was dissolved in methanol (80 ml) and sodium borohydride (0.63 g) was added portionwise to the solution at 0° under nitrogen. The mixture was stirred for 1 h and then 2N hydrochloric acid (40 ml) was added. The solvent was evaporated in vacuo, the residue partitioned between 8% sodium bicarbonate solution (150 ml) and ethyl acetate (100 ml). The organic phase was separated, and the aqueous phase re-extracted with ethyl acetate (100 ml). The combined organic extracts were dried and evaporated in vacuo to give a yellow oil. Purification by FCC eluting with toluene-ethanol-triethylamine (98:2:1) afforded the title compound as a yellow oil (1.59 g).

후처리

  1. filtrationThe mixture was filtered
  2. customthe filtrate evaporated in vacuo
  3. dissolutionThe residue was dissolved in methanol (80 ml)
  4. additionsodium borohydride (0.63 g) was added portionwise to the solution at 0° under nitrogen
  5. addition2N hydrochloric acid (40 ml) was added
  6. customThe solvent was evaporated in vacuo
  7. customthe residue partitioned between 8% sodium bicarbonate solution (150 ml) and ethyl acetate (100 ml)
  8. customThe organic phase was separated
  9. extractionthe aqueous phase re-extracted with ethyl acetate (100 ml)
  10. customThe combined organic extracts were dried
  11. customevaporated in vacuo
  12. customto give a yellow oil
  13. customPurification by FCC
  14. washeluting with toluene-ethanol-triethylamine (98:2:1)

출처 및 근거

ORD 기록
ord-f2cb3e9b2bbf40adb5ca28fc232a6c19
출처 데이터셋
uspto-grants-1990_09
특허 번호
US04959381

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