5-Bromopentanenitrile → HCID 20202803, compound

HRID 543777Notes

Reaction equation

HRID 543777 reaction equation
CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([CH2:14]S(C2C=CC=CC=2)=O)[N:9]=1.Br[CH2:24][CH2:25][CH2:26][CH2:27][C:28]#[N:29].[F:30][C:31]([F:37])([F:36])[CH2:32][N:33]=[C:34]=[S:35]>CN(C=O)C.C1(C)C=CC=CC=1.C(#N)C.O>[F:30][C:31]([F:37])([F:36])[CH2:32][NH:33][C:34](=[S:35])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10](/[CH:14]=[CH:24]/[CH2:25][CH2:26][CH2:27][C:28]#[N:29])[N:9]=1

Participants

9

Reactant 4

HCID 794355-BromopentanenitrileHCID 138837771,1,1-Trifluoro-2-isothiocyanatoethaneHCID 20202779HCID 20202779, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 20202803HCID 20202803, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of potassium t-butoxide (0.88 g.) in DMF (30 ml.) stirred at 0° under nitrogen was added 4-amino-2-phenylsulphinylmethylpyrimidine (1.84 g.). The solution was stirred for 10 minutes and 5-bromo-valeronitrile (1.3 g.) in DMF (5 ml.) added over 5 minutes. The mixture was stirred for 30 minutes at 0°, poured into water (150 ml.) and extracted with EtOAc (4×15 ml.) and the extract dried (MgSO4) and evaporated in vacuo to give a clear gum (1.7 g.). The gum was heated in toluene (40 ml.) at reflux for 30 minutes during which time it dissolved. The toluene was evaporated in vacuo and the residue partitioned between CH2Cl2 and 1 M aqueous hydrochloric acid. The aqueous layer was basified with 4 M aqueous sodium hydroxide and extracted with CH2Cl2 (3×15 ml.), the extract dried (MgSO4) and evaporated in vacuo to give a clear gum (900 mg.). To this gum (900 mg.) in acetonitrile (20 ml.) was added 2,2,2-trifluoroethylisothiocyanate (500 ml.) and the solution heated under reflux for 19 hours. The acetonitrile was evaporated in vacuo and trans-6-[4-(3-[2,2,2-trifluoroethyl]thioureido)pyrimid-2-yl]hex-5-enenitrile was isolated from the mixture by medium pressure chromatography on silica using EtOAc/cyclohexane 3:7 v/v as eluant.

Workup

  1. stirringThe mixture was stirred for 30 minutes at 0°
  2. extractionextracted with EtOAc (4×15 ml.)
  3. dry with materialthe extract dried (MgSO4)
  4. customevaporated in vacuo
  5. customto give a clear gum (1.7 g.)
  6. temperatureat reflux for 30 minutes during which time it
  7. dissolutiondissolved
  8. customThe toluene was evaporated in vacuo
  9. customthe residue partitioned between CH2Cl2 and 1 M aqueous hydrochloric acid
  10. extractionextracted with CH2Cl2 (3×15 ml.)
  11. dry with materialthe extract dried (MgSO4)
  12. customevaporated in vacuo
  13. customto give a clear gum (900 mg.)
  14. temperaturethe solution heated
  15. temperatureunder reflux for 19 hours
  16. customThe acetonitrile was evaporated in vacuo

Sources & evidence

ORD record
ord-856a2a650cd24baab3167bb911aced45
Source dataset
uspto-grants-1984_05
Patent number
US04447441

Reaction notes

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