Diiodomethane → 9-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1628851노트

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HRID 1628851 반응식
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([OH:28])[C:24]([F:27])([F:26])[F:25])=[CH:4][CH:3]=1.C(OC=C)(=O)C.C(=O)([O-])[O-].[Na+].[Na+].C([Zn]CC)C.CCC[CH2:49][CH2:50][CH3:51].ICI>ClC1C=CC=CC=1Cl.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([O:28][CH:49]2[CH2:50][CH2:51]2)[C:24]([F:25])([F:26])[F:27])=[CH:4][CH:3]=1

참가 물질

9

반응물 6

HCID 6346DiiodomethaneHCID 7904Vinyl AcetateHCID 8058HexaneHCID 10340Sodium CarbonateHCID 577861691-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanolHCID 178418750HCID 178418750, 화합물

생성물 1

HCID 577857809-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole수율 37%

시약·촉매·용매 2

HCID 72391,2-Dichlorobenzene용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A suspension of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol (135 mg, 0.300 mmol), vinyl acetate (277 μL, 3.00 mmol), di-μ-chlorobis[(η-cycloocta-1,5-diene)iridium (I)] (50.4 mg, 0.0750 mmol) and sodium carbonate (19.1 mg, 0.180 mmol) in o-dichlorobenzene (3.0 mL) was stirred for 27 h at 100° C. The reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane. The obtained compound was dissolved in dichloromethane (1.6 mL). A solution of diethyl zinc in hexane (1.0 M, 818 μL, 0.818 mmol) and diiodomethane (132 μL, 1.64 mmol) was added at 0° C. After being stirred for 4 h at room temperature, the reaction mixture was diluted with ethyl acetate, quenched with aqueous ammonium chloride, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (62.9 mg, 0.110 mmol, 37%). Analytically pure material was obtained by recrystallization from ethyl acetate/hexane.

후처리

  1. customThe reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane
  2. dissolutionThe obtained compound was dissolved in dichloromethane (1.6 mL)
  3. stirringAfter being stirred for 4 h at room temperature
  4. customquenched with aqueous ammonium chloride
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture

출처 및 근거

ORD 기록
ord-2445ddacb8c44aabbd8c1bdd476bf28a
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785460B2

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