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

HRID 871177ノート

反応式

HRID 871177 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f32351a0334c4feebf6afb17a904c446
出典データセット
uspto-grants-2015_03
特許番号
US08969586B2

反応ノート

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