2,2'-Bipyridine → 10-Chloro-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

HRID 1628649노트

반응식

HRID 1628649 반응식
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:4][CH:3]=1.Br[C:22]1[C:27]([Cl:28])=[CH:26][C:25]([C:29]([F:32])([F:31])[F:30])=[CH:24][N:23]=1.N1C=CC=CC=1C1C=CC=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.C(OCC)(=O)C.[Cu]I>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:22]4[C:27]([Cl:28])=[CH:26][C:25]([C:29]([F:32])([F:30])[F:31])=[CH:24][N:23]=4)[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:4][CH:3]=1

참가 물질

8

반응물 4

HCID 14742,2'-BipyridineHCID 10796Cesium carbonateHCID 27362372-Bromo-3-chloro-5-(trifluoromethyl)pyridineHCID 13610182510-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

생성물 1

HCID 5778593810-Chloro-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole수율 43.3%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
150 °C

실험 절차

A mixture of 10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (Reference Example 72; 150 mg, 0.51 mmol), 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (401 mg, 1.54 mmol), copper(I) iodide (97 mg, 0.51 mmol), 2,2′-bipyridyl (159 mg, 1.02 mmol) and cesium carbonate (333 mg, 1.02 mmol) in 1-methyl-2-pyrrolidinone (2.0 mL) was stirred at 150° C. for 16 hr. The mixture was diluted with ethyl acetate, filtered through a pad of celite, washed with 2N hydrochloric acid, water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a residue, which was purified by preparative HPLC to give a solid, which was recrystallized from n-hexane/ethyl acetate to give the title compound (104 mg, 0.221 mmol, 43%) as a colorless solid.

후처리

  1. filtrationfiltered through a pad of celite
  2. washwashed with 2N hydrochloric acid, water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give a residue, which
  8. customwas purified by preparative HPLC
  9. customto give a solid, which
  10. customwas recrystallized from n-hexane/ethyl acetate

출처 및 근거

ORD 기록
ord-d19bc92bdcf3430abbb9c3e0afbc5c22
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785460B2

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