1,4-Dioxane → 5-Benzo[b]thien-7-yl-4-methylpyrimidine

HRID 593773Notes

Reaction equation

HRID 593773 reaction equation
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

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 120455387-Bromobenzo[b]thiopheneHCID 66521275HCID 66521275, compound

Product 1

HCID 867304295-Benzo[b]thien-7-yl-4-methylpyrimidineYield 30.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0159a724358c42499627312456a68d49
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

Loading…