Triethylamine → 1-Tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine

HRID 1354250노트

반응식

HRID 1354250 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[F:29][C:30]1[C:39]([F:40])=[CH:38][C:33]2[N:34]=[C:35]([SH:37])[NH:36][C:32]=2[CH:31]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>C1COCC1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:37][C:35]2[NH:36][C:32]3[CH:31]=[C:30]([F:29])[C:39]([F:40])=[CH:38][C:33]=3[N:34]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

9

반응물 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 31297Methanesulfonyl chlorideHCID 735736Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 106791065,6-difluoro-1H-benzimidazole-2-thiol

생성물 1

HCID 117110271-Tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine수율 68%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 1-tert-butoxycarbonyl-4-(2-hydroxyethyl)piperazine (7.40 g, 32.13 mmol) in THF (100 mL), while stirring in an ice-bath, triethylamine (4.36 g, 43.09 mmol), 4-dimethylaminopyridine (200 mg, 1.64 mmol), and methanesulfonyl chloride (7.40 g, 38.76 mmol) were sequentially added. The temperature of the mixture was allowed to room temperature, and the mixture was stirred for 50 minutes. The reaction mixture was filtrated, and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (200 mL), and, at room temperature, 5,6-difluoro-2-mercaptobenzimidazole (5.00 g, 26.86 mmol), potassium carbonate (8.64 g, 62.51 mmol), and 18-crown-6 (500 mg, 1.92 mmol) were sequentially added to the solution, followed by stirring for 90 minutes at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1). The product was crystallized from acetone-ether-hexane, to thereby yield 1-tert-butoxycarbonyl-4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazine (7.26 g, yield 68%) as colorless crystals.

후처리

  1. customwas allowed to room temperature
  2. filtrationThe reaction mixture was filtrated
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (200 mL)
  5. stirringby stirring for 90 minutes at 80° C
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe residue was purified through silica gel column chromatography (silica gel 200 g, hexane: acetone=8:1 to 1:1)
  8. customThe product was crystallized from acetone-ether-hexane

출처 및 근거

ORD 기록
ord-afd6da84661d43fa9da70f4253b5befa
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07223764B2

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