4-Aminobenzonitrile → 2-(4-Cyanophenylamino)-2-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]thioacetamide

HRID 2089681Notes

Reaction equation

HRID 2089681 reaction equation
[F:1][C:2]1[C:9]([O:10][CH2:11][CH2:12][OH:13])=[CH:8][C:7]([O:14][CH3:15])=[CH:6][C:3]=1[CH:4]=O.[NH2:16][C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1.C[Si]([C:29]#[N:30])(C)C.[NH4+]=[S:32]>CO.Cl.NC(N)=N.C(OCC)(=O)C.O1CCCC1>[C:21]([C:20]1[CH:23]=[CH:24][C:17]([NH:16][CH:4]([C:3]2[CH:6]=[C:7]([O:14][CH3:15])[CH:8]=[C:9]([O:10][CH2:11][CH2:12][OH:13])[C:2]=2[F:1])[C:29]([NH2:30])=[S:32])=[CH:18][CH:19]=1)#[N:22]

Participants

8

Reactant 3

HCID 133964-AminobenzonitrileHCID 82115Trimethylsilyl cyanideHCID 866774082-Fluoro-3-(2-hydroxyethoxy)-5-methoxybenzaldehyde

Product 1

HCID 866774072-(4-Cyanophenylamino)-2-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]thioacetamide

Reagents, catalysts & solvents 4

HCID 5742Guanidine HydrochlorideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

Under nitrogen atmosphere, to a solution of the crude product containing 2-fluoro-3-(2-hydroxyethoxy)-5-methoxybenzaldehyde (16.68 g, 77.9 mmol), 4-aminobenzonitrile (9.20 g, 77.9 mmol), and guanidine hydrochloride (372 mg, 3.9 mmol) in methanol (132 mL), trimethylsilylcyanide (12.09 g, 116.9 mmol) was added at room temperature, and the resulting mixture was stirred at 40° C. for 19 hours. After cooling the mixture, tetrahydrofuran (132 mL) was added thereto under water cooling, and 20% aqueous ammonium sulfide solution (133 mL) was added dropwise to the resulting mixture, after which the resulting mixture was stirred at room temperature. After completion of the reaction, ethyl acetate and 5% saline were added to the reaction mixture, and the resulting mixture was extracted. The organic layer was washed with 5% saline and then concentrated under reduced pressure. Methanol (100 mL) was added to the residue obtained, and the resulting mixture was concentrated under reduced pressure. Further, methanol (100 mL) was added to the residue obtained, and the resulting mixture was concentrated under reduced pressure. Methanol (120 mL) was added to the residue obtained, and the resulting mixture was stirred overnight at room temperature. The precipitated solid was filtered and dried to obtain the captioned compound (20.46 g) as a pale purple solid.

Workup

  1. additionwas added at room temperature
  2. additionwas added
  3. stirringafter which the resulting mixture was stirred at room temperature
  4. additionwere added to the reaction mixture
  5. extractionthe resulting mixture was extracted
  6. washThe organic layer was washed with 5% saline
  7. concentrationconcentrated under reduced pressure
  8. additionMethanol (100 mL) was added to the residue
  9. customobtained
  10. concentrationthe resulting mixture was concentrated under reduced pressure
  11. additionFurther, methanol (100 mL) was added to the residue
  12. customobtained
  13. concentrationthe resulting mixture was concentrated under reduced pressure
  14. additionMethanol (120 mL) was added to the residue
  15. customobtained
  16. stirringthe resulting mixture was stirred overnight at room temperature
  17. filtrationThe precipitated solid was filtered
  18. customdried

Sources & evidence

ORD record
ord-409c754209124d2baea1a34661fd99b5
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

Loading…