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

HRID 871173Notes

Reaction equation

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.[F: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:16]3[CH:15]=[CH:14][C:13]([F:12])=[CH:18][C:17]=3[F:19])=[CH:3][S:4][C:5]=12

Participants

Conditions

Temperature: 90 °C

Procedure

A vessel capable of sealing was charged with a mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine (110 mg, 0.443 mmol), 2,4-difluorophenylboronic acid (84 mg, 0.531 mmol), PdCl2(dppf)-CH2Cl2 adduct (18.1 mg, 0.022 mmol), dioxane (3 mL), and a 2.0 M aqueous solution of K3PO4 (0.66 mL, 1.328 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 3 hours. 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 30%-60% CH2Cl2/hexanes at 30 mL/min. Concentration of appropriate fractions provided the title compound (450 mg, 49% yield) as a white powder. LC/MS: Example 102A @ 3.60 min (RT) (Condition G). MS (ES): m/z=282.02/284.02, [M+H]+.

Workup

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

Sources & evidence

ORD record: ord-5459e006487a4f3bb4269a29fac2c772
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969586B2

Reaction notes

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