1,4-Dioxane → 7-Chloro-3-(2-chloro-4-fluorophenyl)thieno[3,2-b]pyridine

HRID 593771노트

반응식

HRID 593771 반응식
Br[C:2]1[C:6]2=[N:7][CH:8]=[CH:9][C:10]([Cl:11])=[C:5]2[S:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].C(Cl)Cl>[Cl:11][C:10]1[CH:9]=[CH:8][N:7]=[C:6]2[C:2]([C:14]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=3[Cl:12])=[CH:3][S:4][C:5]=12

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 177502292-Chloro-4-fluorobenzeneboronic acidHCID 867304243-Bromo-7-chlorothieno[3,2-b]pyridine

생성물 1

HCID 867304277-Chloro-3-(2-chloro-4-fluorophenyl)thieno[3,2-b]pyridine수율 80.2%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매

반응 조건

온도
90 °C

실험 절차

A vessel capable of sealing was charged with a mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine (260 mg, 1.046 mmol), 2-chloro-4-fluorophenylboronic acid (274 mg, 1.569 mmol), PdCl2(dppf)-CH2Cl2 adduct (42.7 mg, 0.0.052 mmol), dioxane (8 mL), and a 2.0 M aqueous solution of K3PO4 (1.6 mL, 3.14 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 3 h. Upon cooling, the reaction mixture was diluted with water and extracted with CH2Cl2. The combined organics were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 60%-100% CH2Cl2/hexanes at 30 mL/min. Concentration of appropriate fractions provided the title compound (250 mg, 80% yield) as a white solid. LC/MS: Example 103A @ 3.58 min (RT) (Condition G). MS (ES): m/z=297.89, [M+H]+.

후처리

  1. customThe vessel was sealed
  2. temperatureUpon cooling
  3. extractionextracted with CH2Cl2
  4. washThe combined organics were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by BIOTAGE®
  8. washeluting with 60%-100% CH2Cl2/hexanes at 30 mL/min

출처 및 근거

ORD 기록
ord-d8c004f8b3b142b2bd9ffab363fdaf85
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242967B2

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