Dichloromethane → N-{4-[4-(4-chlorophenyl)-4-hydroxy-4,5,6,7-tetrahydro-1-benzothien-2-yl]pyridin-2-yl}acetamide

HRID 1615489노트

반응식

HRID 1615489 반응식
Br[C:2]1[S:3][C:4]2[CH2:10][CH2:9][CH2:8][C:7]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)([OH:11])[C:5]=2[CH:6]=1.O1CCOCC1.C[Sn](C)(C)[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=1.ClCCl>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:7]2([OH:11])[C:5]3[CH:6]=[C:2]([C:27]4[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=4)[S:3][C:4]=3[CH2:10][CH2:9][CH2:8]2)=[CH:13][CH:14]=1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 312751,4-DioxaneHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 681832292-Bromo-4-(4-chlorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-ol

생성물 1

HCID 68182981N-{4-[4-(4-chlorophenyl)-4-hydroxy-4,5,6,7-tetrahydro-1-benzothien-2-yl]pyridin-2-yl}acetamide수율 10%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매

실험 절차

In a 100 mL round bottomed flask were placed 2-bromo-4-(4-chlorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-ol (640 mg, 1.9 mmol) and 1,4-dioxane (10 mL). To the mixture were added N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (925 mg, 3.09 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (198 mg, 0.242 mmol). The mixture was refluxed for 16 hr with vigorous stirring. The mixture was allowed to cool to rt and then diluted with EtOAc (100 mL). The resulting solution was washed with H2O (50 mL×2). The combined aqueous phases were extracted with EtOAc (50 mL×2). The combined organic phases were washed with brine (50 mL) and dried over MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by pre-packed silica gel (40 g) column chromatography, eluting with a 30% to 100% EtOAc/hexane to obtain crude title compound (ca 500 mg). About 100 mg of this material was purified by HPLC (AA) to obtain pure title compound (74 mg; 10%). LCMS: (AA) ES+ 399, 401; 1H NMR (400 MHz, d6-DMSO) δ ppm 10.51 (br s, 1H), 8.23 (s, 1H), 8.20 (d, 1H), 7.36 (d, 2H), 7.30 (d, 2H), 7.19 (dd, 1H), 7.14 (s, 1H), 5.85 (s, 1H), 2.83-2.90 (m, 2H), 2.07 (s, 3H), 1.85-2.01 (m, 3H), 1.65-1.70 (m, 1H).

후처리

  1. customIn a 100 mL round bottomed flask were placed
  2. temperatureThe mixture was refluxed for 16 hr with vigorous stirring
  3. washThe resulting solution was washed with H2O (50 mL×2)
  4. extractionThe combined aqueous phases were extracted with EtOAc (50 mL×2)
  5. washThe combined organic phases were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. customInsoluble materials were removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by pre-packed silica gel (40 g) column chromatography
  10. washeluting with a 30% to 100% EtOAc/hexane
  11. customto obtain crude title compound (ca 500 mg)
  12. customAbout 100 mg of this material was purified by HPLC (AA)

출처 및 근거

ORD 기록
ord-e840a850f62145f292f28eb848e7eb86
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765746B2

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