Dimethylformamide → HCID 60204533, compound

HRID 2267404Notes

Reaction equation

HRID 2267404 reaction equation
Br[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][N:16]2[C:20]([CH3:22])([CH3:21])[C:19](=[O:23])[NH:18][C:17]2=[O:24])[N:8]=1.[Cu][C:26]#[N:27].CN(C=O)C>Cl.[Fe](Cl)(Cl)Cl>[CH3:21][C:20]1([CH3:22])[N:16]([CH2:15][CH2:14][NH:13][C:9]2[N:8]=[C:7]([C:3]3[S:4][CH:5]=[CH:6][C:2]=3[C:26]#[N:27])[CH:12]=[CH:11][N:10]=2)[C:17](=[O:24])[NH:18][C:19]1=[O:23]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 68501127HCID 68501127, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 60204533HCID 60204533, compound

Reagents, catalysts & solvents 2

HCID 24380Iron chloride (FeCl3)CatalystHCID 313Hydrochloric AcidSolvent

Conditions

Temperature
160 °C

Procedure

A round-bottomed flask equipped with a nitrogen inlet and a reflux condenser was charged with 1-(2-(4-(3-bromothiophen-2-yl)pyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazol-idine-2,4-dione (50 mg, 0.12 mmol), copper (I) cyanide (33 mg, 0.36 mmol), and dry DMF (2 mL). The reaction mixture was heated to reflux (bath temperature 160° C.). After 4 h, the reaction vessel was removed from the oil bath and allowed to cool to approximately 70° C. and poured into a stirring suspension of iron (III) chloride (0.28 g, 1.70 mmol) in 1.7 N aqueous HCl (5.0 mL). The combined mixture was maintained at 60-70° C. for 30 min at which time the mixture was allowed to cool to ambient temperature and extracted with three 15 mL portions of dichloromethane. The combined extracts were washed with two 40 mL portions of 6 N aqueous HCl, saturated aqueous NaHCO3, and H2O, then dried over Na2SO4 and concentrated. Chromatographic purification by preparative TLC, eluting with 8% MeOH/dichloromethane, and subsequent crystallization from EtOAc afforded the product as a white solid. MS (M+H)+ 357.

Workup

  1. customA round-bottomed flask equipped with a nitrogen inlet and a reflux condenser
  2. temperatureThe reaction mixture was heated
  3. customthe reaction vessel was removed from the oil bath
  4. temperatureto cool to approximately 70° C.
  5. temperatureThe combined mixture was maintained at 60-70° C. for 30 min at which time the mixture
  6. temperatureto cool to ambient temperature
  7. extractionextracted with three 15 mL portions of dichloromethane
  8. washThe combined extracts were washed with two 40 mL portions of 6 N aqueous HCl, saturated aqueous NaHCO3, and H2O
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customChromatographic purification by preparative TLC
  12. washeluting with 8% MeOH/dichloromethane, and subsequent crystallization from EtOAc

Sources & evidence

ORD record
ord-1cb7380917364a4691a30afaa37428e5
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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