Ammonia → (4-chloro-benzyl)-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-amine

HRID 1754724노트

반응식

HRID 1754724 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[N:6][C:7]=1[F:8].C([Li])CCC.Cl[Si](C)(C)CC[Si](Cl)(C)C.C([Li])(C)(C)C.C([Cu])#N.C(OC([N:48]1[C:52]2=[N:53][CH:54]=[C:55]([Cl:57])[CH:56]=[C:51]2[C:50]([CH2:58]Cl)=[CH:49]1)=O)(C)(C)C.Cl.N>O1CCCC1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][NH:9][C:5]2[CH:4]=[CH:3][C:2]([CH2:58][C:50]3[C:51]4[C:52](=[N:53][CH:54]=[C:55]([Cl:57])[CH:56]=4)[NH:48][CH:49]=3)=[C:7]([F:8])[N:6]=2)=[CH:12][CH:13]=1

참가 물질

10

반응물 8

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 835521,2-Bis(chlorodimethylsilyl)ethaneHCID 57619198(5-Bromo-6-fluoro-pyridin-2-yl)-(4-chloro-benzyl)-amineHCID 576192411-Boc-5-chloro-3-(chloromethyl)-7-azaindoleHCID 178418306HCID 178418306, 화합물HCID 178418339ButyllithiumHCID 178418546HCID 178418546, 화합물

생성물 1

HCID 24956037(4-chloro-benzyl)-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-amine수율 33.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매4회

실험 절차

To (5-bromo-6-fluoro-pyridin-2-yl)-(4-chloro-benzyl)-amine (537, 2.76 g, 8.75 mol) in tetrahydrofuran (90.0 mL), under an atmosphere of nitrogen at −78° C., n-butyllithium (2.50 M in hexane, 3.64 mL) was added slowly. After 60 minutes, 1,2-bis-(chloro-dimethyl-silanyl)-ethane (0.942 g, 4.38 mol) in tetrahydrofuran (8.0 mL) was added to the reaction. The reaction mixture was allowed to stir at room temperature for 2 hours. The reaction was cooled to −78° C., followed by addition of tert-butyllithium (1.70 M in hexane, 10.50 mL). The reaction was stirred for 30 minutes, followed by addition of 0.65 M of CuCN.2LiCl in tetrahydrofuran (14.0 mL). The reaction was stirred at −35° C. for 10 minutes, followed by addition of 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (535, 1.70 g, 5.64 mol, prepared as described in Example 49, Scheme 164) in tetrahydrofuran (10.0 mL). The reaction was allowed to warm to room temperature for 1 hour and 2 N HCl (30 mL) was added to the reaction mixture, then stirred for 30 minutes. The reaction was poured into aqueous ammonia 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 30% ethyl acetate in hexane to give the desired compound (P-0132, 0.75 g, 33.1%). MS (ESI) [M+H+]+=401.1.

후처리

  1. temperatureThe reaction was cooled to −78° C.
  2. stirringThe reaction was stirred for 30 minutes
  3. stirringThe reaction was stirred at −35° C. for 10 minutes
  4. temperatureto warm to room temperature for 1 hour
  5. stirringstirred for 30 minutes
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. custompurified with silica gel column chromatography
  11. washeluting with 30% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-087a6e491b294974b251c9cbb255c79f
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169250B2

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