1,4-Dioxane → 5-benzo[b]thien-7-yl-4-methylPyrimidine

HRID 871177노트

반응식

HRID 871177 반응식
Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:11][C:12]1[C:17](B(O)O)=[CH:16][N:15]=[CH:14][N:13]=1.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.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.O>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:17]3[C:12]([CH3:11])=[N:13][CH:14]=[N:15][CH:16]=3)[C:7]1=2

참가 물질

8

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 120455387-Bromobenzo[b]thiopheneHCID 66521275(4-Methylpyrimidin-5-YL)boronic acid

생성물 1

HCID 867304295-benzo[b]thien-7-yl-4-methylPyrimidine수율 30.3%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
100 °C

실험 절차

A vessel capable of sealing was charged with a mixture of 7-bromobenzo[b]thiophene (100 mg, 0.467 mmol), 4-methylpyrimidin-5-ylboronic acid (97 mg, 0.70 mmol), PdCl2(dppf)-CH2Cl2 adduct (19.2 mg, 0.023 mmol), dioxane (3 mL), and a 2.0 M water solution of K3PO4 (0.7 mL, 1.41 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 100° C. for 16 hours. Upon cooling, the reaction mixture was diluted with CH2Cl2 and filtered with CH2Cl2/MeOH washing. The filtrate was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 0%-15% EtOAc/CH2Cl2 at 30 mL/min. Concentration of appropriate fractions provided the title compound (32 mg, 30% yield). LC/MS: Example 108A @ 2.49 min (RT) (Condition G). MS (ES): m/z=227.07.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 9.19 (1 hr, s), 8.68 (1 hr, s), 7.92 (1 hr, d, J=8.06 Hz), 7.38-7.52 (3 hr, m), 7.23 (1 hr, d, J=7.05 Hz), 2.44 (3 hr, s).

후처리

  1. customThe vessel was sealed
  2. temperatureUpon cooling
  3. filtrationfiltered with CH2Cl2/MeOH washing
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. washwashed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by BIOTAGE®
  10. washeluting with 0%-15% EtOAc/CH2Cl2 at 30 mL/min

출처 및 근거

ORD 기록
ord-f32351a0334c4feebf6afb17a904c446
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969586B2

반응 노트

불러오는 중…