Morpholine → 2-[4-(3-chloropyridin-2-yl)phenyl]-6-morpholin-4-yl-1H-benzoimidazole

HRID 1497487노트

반응식

HRID 1497487 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)=[CH:12][CH:11]=3)[NH:7][C:6]=2[CH:23]=1.CN(C(C(C)C)C)C.C[Si](C)(C)CCOCCl.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>ClCCl.C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:22][C:21]1[C:16]([C:13]2[CH:14]=[CH:15][C:10]([C:8]3[NH:7][C:6]4[CH:23]=[C:2]([N:41]5[CH2:46][CH2:45][O:44][CH2:43][CH2:42]5)[CH:3]=[CH:4][C:5]=4[N:9]=3)=[CH:11][CH:12]=2)=[N:17][CH:18]=[CH:19][CH:20]=1

참가 물질

9

반응물 5

HCID 8083MorpholineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 117179436-bromo-2-(4-(3-chloropyridin-2-yl)phenyl)-1H-benzoimidazoleHCID 22949790N,N,3-Trimethylbutan-2-amine

생성물 1

HCID 116682682-[4-(3-chloropyridin-2-yl)phenyl]-6-morpholin-4-yl-1H-benzoimidazole수율 98.1%

시약·촉매·용매 3

HCID 1140Toluene용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 162 mg (0.42 mmol) 6-bromo-2-(4-(3-chloropyridin-2-yl)phenyl)-1H-benzoimidazole in 6 mL dichloromethane were added 0.2 mL (1.15 mmol) N,N-dimethylisopropylethylamine and 0.1 mL (0.57 mmol) 2-(trimethylsilyl)ethoxymethyl chloride, followed by stirring at room temperature for 16 hours. After vacuum concentration, 26 μL (0.30 mmol) morpholine, 56.3 mg (0.013 mmol) tris(dibenzylidine acetone)dipalladium(0), 10 mg (0.038 mmol) 2-(di-t-butylphosphino)biphenyl, and 38.8 mg (0.41 mmol) sodium-t-botoxide were added to the concentrate, which was then dissolved in 2.5 mL toluene and allowed to react at 90° C. for 10 min in a microwave reactor. After being cooled to room temperature, the product was dissolved in 5 mL ethyl acetate and filtered with diatomite. The filtrate was dried over magnesium sulfate and vacuum concentrated. The concentrate was dissolved in 3 mL of a mixture of trifluoro fluoroacetic acid and methylene:chloride (1:1) and stirred for 12 hours. Neutralization with 10% NaOH, extraction with ethyl acetate, drying with magnesium sulfate and vacuum concentration were sequentially conducted in that order. The residue thus obtained was separated using column chromatography (developing solvent: hexane/ethyl acetate=1/1) to produce 115 mg of 2-[4-(3-chloropyridin-2-yl)phenyl]-6-morpholin-4-yl-1H-benzoimidazole (yield 70%).

후처리

  1. additionwere added to the concentrate, which
  2. customto react at 90° C. for 10 min in a microwave reactor
  3. temperatureAfter being cooled to room temperature
  4. filtrationfiltered with diatomite
  5. dry with materialThe filtrate was dried over magnesium sulfate and vacuum
  6. concentrationconcentrated
  7. dissolutionThe concentrate was dissolved in 3 mL of a mixture of trifluoro fluoroacetic acid and methylene:chloride (1:1)
  8. stirringstirred for 12 hours
  9. extractionNeutralization with 10% NaOH, extraction with ethyl acetate
  10. dry with materialdrying with magnesium sulfate and vacuum concentration
  11. customThe residue thus obtained
  12. customwas separated

출처 및 근거

ORD 기록
ord-eec35884170744d585395b6ecd011ee2
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199965B2

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