Acetic Acid → HCID 58094781, compound

HRID 2282132Notes

Reaction equation

HRID 2282132 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]([NH:20][C:21](=[O:23])[CH3:22])[CH:15]=2)=[CH:11][C:10]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])C=C.C(O)(=O)C.C1([SiH3])C=CC=CC=1>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:31][C:25]1[CH:26]=[C:27]([Cl:30])[CH:28]=[CH:29][C:24]=1[C:10]1[CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][C:21](=[O:23])[CH3:22])[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 58094981HCID 58094981, compound

Product 1

HCID 58094781HCID 58094781, compoundYield 85.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-{4-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]pyridin-2-yl}acetamide (750 mg, 1.60 mmol) and tetrakis(triphenylphosphine)palladium (92.0 mg, 0.08 mmol) in DCM (12.0 mL) was added acetic acid (3.95 mL, 69.5 mmol) and phenylsilane (1.00 mL, 8.15 mmol) and the mixture was stirred for 24 hrs at 40° C. The reaction mixture was evaporated to remove volatiles and DCM added. To this solution was added saturated NaHCO3 and the resulting mixture was stirred for 30 min. The mixture was extracted with DCM (3×100 mL) and the combined DCM layers were washed with brine. The organics were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was partially purified by column chromatography (SiO2, elution with 3-6% MeOH in DCM) to give crude product which was further purified by column chromatography (SiO2, elution with 100% EtOAc) to provide 589 mg of the product (84%). LC/MS (FA) ES+ 431. 1H NMR (400 MHz, d6 DMSO) δ: 11.8-11.9 (br s, 1H), 10.6 (s, 1H), 8.39 (s, 1H), 8.32 (d, J=5.2 Hz, 1H), 7.71 (d, J=1.7 Hz, 1H), 7.69 (s, 1H), 7.45-7.49 (m, 2H), 7.42 (d, J=8.5 Hz, 1H), 6.90-7.15 (br s, 2H), 2.12 (s, 3H).

Workup

  1. customThe reaction mixture was evaporated
  2. customto remove volatiles and DCM
  3. additionadded
  4. additionTo this solution was added saturated NaHCO3
  5. stirringthe resulting mixture was stirred for 30 min
  6. extractionThe mixture was extracted with DCM (3×100 mL)
  7. washthe combined DCM layers were washed with brine
  8. dry with materialThe organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was partially purified by column chromatography (SiO2, elution with 3-6% MeOH in DCM)
  12. customto give crude product which
  13. customwas further purified by column chromatography (SiO2, elution with 100% EtOAc)

Sources & evidence

ORD record
ord-65dc26e3162d4574ab8c96c73b9553e9
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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