Acetic Acid → HCID 58095178, compound

HRID 2282135Notes

Reaction equation

HRID 2282135 reaction equation
C([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=2)=[CH:11][C:10]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[Cl:28])C=C.C1([SiH3])C=CC=CC=1.C(O)(=O)C>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:28][C:22]1[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:21]=1[C:10]1[CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=2)[S:13][C:9]=1[C:5]1[NH:6][CH:7]=[CH:8][N:4]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 12752PhenylsilaneHCID 58094898HCID 58094898, compound

Product 1

HCID 58095178HCID 58095178, compoundYield 50.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 4-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]-2-methylpyridine (115 mg, 0.26 mmol) in DCM (10.0 mL) was added phenylsilane (0.16 mL, 1.28 mmol), acetic acid (0.66 mL, 11.5 mmol), and tetrakis(triphenylphosphine)palladium (14.8 mg, 0.01 mmol) at room temperature then the mixture was stirred for 2 h at 40° C. After cooling to room temperature, the solvent was evaporated under reduced pressure and the residual acetic acid was quenched by addition of saturated NaHCO3 (50 mL). The mixture was extracted with DCM (3×70 mL), and the combined DCM layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, elution with 3-5% MeOH in DCM) to give crude product which was further purified by column chromatography (SiO2, elution with 100% EtOAc) to provide 51 mg of product (49% yield). LC/MS (FA) ES+ 388. 1H NMR (400 MHz, d6 DMSO) δ: 11.7 (br s, 1H), 8.46 (d, J=5.3 Hz, 1H), 7.76 (s, 1H), 7.72 (d, J=2.1 Hz, 1H), 7.57 (br s, 1H), 7.46-7.50 (m, 2H), 7.41 (d, J=8.3 Hz, 1H), 7.10 (br s, 1H), 6.95 (br s, 1H), 2.49 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was evaporated under reduced pressure
  3. customthe residual acetic acid was quenched by addition of saturated NaHCO3 (50 mL)
  4. extractionThe mixture was extracted with DCM (3×70 mL)
  5. dry with materialthe combined DCM layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, elution with 3-5% MeOH in DCM)
  9. customto give crude product which
  10. customwas further purified by column chromatography (SiO2, elution with 100% EtOAc)

Sources & evidence

ORD record
ord-4645bf9d462d46f3b161d84fd506ced5
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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