1,2-Bis(chlorodimethylsilyl)ethane → 3-[6-(4-Chloro-benzylamino)-pyridazin-3-ylmethyl]-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 1367344노트

반응식

HRID 1367344 반응식
Br[C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.C([Li])CCC.Cl[Si](C)(C)CC[Si](Cl)(C)C.C([Li])(C)(C)C.C([Cu])#N.[C:40]([O:44][C:45]([N:47]1[C:51]2=[N:52][CH:53]=[CH:54][CH:55]=[C:50]2[C:49]([CH2:56]Cl)=[CH:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>O1CCCC1.CCCCCC.O>[C:40]([O:44][C:45]([N:47]1[C:51]2=[N:52][CH:53]=[CH:54][CH:55]=[C:50]2[C:49]([CH2:56][C:2]2[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)=[CH:4][CH:3]=2)=[CH:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]

참가 물질

10

반응물 6

HCID 835521,2-Bis(chlorodimethylsilyl)ethaneHCID 21463021tert-Butyl 3-(chloromethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylateHCID 57619288(6-Bromo-pyridazin-3-yl)-(4-chloro-benzyl)-amineHCID 178418306HCID 178418306, 화합물HCID 178418339ButyllithiumHCID 178418546HCID 178418546, 화합물

생성물 1

HCID 576192483-[6-(4-Chloro-benzylamino)-pyridazin-3-ylmethyl]-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester수율 23.8%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매4회HCID 8058Hexane용매

실험 절차

To (6-bromo-pyridazin-3-yl)-(4-chloro-benzyl)-amine (522, 0.560 g, 1.88 mmol) in tetrahydrofuran (45.0 mL), under an atmosphere of nitrogen at −78° C., was added n-butyllithium (2.50 M in hexane, 0.760 mL) slowly. After 10 minutes, 1,2-bis-(chloro-dimethyl-silanyl)-ethane (0.201 g, 0.94 mmol) in tetrahydrofuran (5.0 mL) was added to the reaction. The reaction mixture was allowed to stir at room temperature for 3 hours. The reaction was cooled to −78° C., followed by addition of 1.70 M of tert-butyllithium in hexane (1.20 mL) slowly. The reaction was stirred for 20 minutes, followed by addition of a solution of CuCN.2LiCl (0.6 M in tetrahydrofuran, 3.00 mL) and 3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (512, 0.47 g, 1.8 mol) in tetrahydrofuran (10.0 mL). After 30 minutes, the reaction was allowed to warm to room temperature for 10 minutes. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was treated with trifluoroacetic acid (1.0 mL) dissolved in dichloromethane (10.0 mL) for 10 minutes. The reaction was concentrated, poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified with silica gel column chromatography eluting with 60% ethyl acetate in hexane to give the desired compound (523, 0.10 g, 23.8%). MS (ESI) [M+H+]+=450.1.

후처리

  1. temperatureThe reaction was cooled to −78° C.
  2. stirringThe reaction was stirred for 20 minutes
  3. waitAfter 30 minutes
  4. temperatureto warm to room temperature for 10 minutes
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. additionThe filtrate was treated with trifluoroacetic acid (1.0 mL)
  9. dissolutiondissolved in dichloromethane (10.0 mL) for 10 minutes
  10. concentrationThe reaction was concentrated
  11. additionpoured into aqueous potassium carbonate
  12. extractionextracted with ethyl acetate
  13. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated
  16. custompurified with silica gel column chromatography
  17. washeluting with 60% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-976f72ef0700447da6574d56c153b82d
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893075B2

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