Acetic Acid → HCID 131731733, compound

HRID 2401777Notes

Reaction equation

HRID 2401777 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]=[CH:16][CH:15]=2)=[N:11][C:10]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)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>[ClH:27].[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:10]2[N:11]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[S:13][C:9]=2[C:5]2[NH:4][CH:8]=[CH:7][N:6]=2)=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 12752PhenylsilaneHCID 66749253HCID 66749253, compound

Product 1

HCID 131731733HCID 131731733, compoundYield 116.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 5-(1-allyl-1H-imidazol-2-yl)-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole (99.0 mg, 0.252 mmol) and tetrakis(triphenylphosphine)palladium (14.6 mg, 0.0126 mmol) in DCM (3.38 mL) was added acetic acid (0.623 mL, 11.0 mmol) and phenylsilane (0.158 mL, 1.28 mmol) and the mixture was stirred for 2 h at 40° C. The reaction mixture was evaporated to remove volatiles and DCM (10 mL) added. To this solution was added saturated sodium bicarbonate (4 mL) and the resulting mixture was stirred for 30 min. The mixture was extracted with DCM (3×10 mL) and the combined DCM layers were washed with brine. The organics were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (methanol/DCM=0/100→10/90) to give 57 mg of the title compound as a yellow solid (64% yield). The HCl salt was made as follows. To a mixture of the free base (57 mg, 0.162 mmol) in ethanol (5 mL) was added 1.0 M HCl in ether (0.178 mL, 0.178 mmol) and the mixture was stirred for 2 hours then concentrated in vacuo. The residue was taken up in a minimum of methanol, and acetonitrile was added to give a precipitate. Ether was added and the precipitate was filtered, washed with ether and dried to give the title compound as an orange solid. LC/MS (FA) ES+ 353. 1H NMR (400 MHz, d6-DMSO) δ: 8.78-8.74 (m, 2H), 7.96-7.91 (m, 2H), 7.48-7.43 (m, 2H), 7.34-7.28 (m, 4H), 4.51 (s, 2H).

Workup

  1. customThe reaction mixture was evaporated
  2. customto remove volatiles and DCM (10 mL)
  3. additionadded
  4. additionTo this solution was added saturated sodium bicarbonate (4 mL)
  5. stirringthe resulting mixture was stirred for 30 min
  6. extractionThe mixture was extracted with DCM (3×10 mL)
  7. washthe combined DCM layers were washed with brine
  8. dry with materialThe organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel chromatography (methanol/DCM=0/100→10/90)

Sources & evidence

ORD record
ord-612173f9155e4251ba254d748c6e4e6f
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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