HCID 67235487, compound → HCID 68322479, compound

HRID 1505384Notes

Reaction equation

HRID 1505384 reaction equation
[CH3:1][CH2:2][Mg+].[Br-].I[C:6]1[CH:13]=[C:12]([O:14][C:15]2[N:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][N:16]=2)[CH:11]=[CH:10][C:7]=1[C:8]#[N:9]>C1COCC1.[Cl-].[Cl-].[Zn+2]>[CH2:1]([C:6]1[CH:13]=[C:12]([O:14][C:15]2[N:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][N:16]=2)[CH:11]=[CH:10][C:7]=1[C:8]#[N:9])[CH3:2]

Participants

5

Reactant 2

HCID 67235487HCID 67235487, compound2×HCID 178461630HCID 178461630, compound

Product 1

HCID 68322479HCID 68322479, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

In a flamed 2-necked flask, under N2, to a solution of ZnCl2 (0.82 mL of a 0.5 M solution on THF, 0.41 mmol) in 1.0 mL of THF, cooled at −15° C., EtMgBr (0.41 mL of a 1.0 M solution in THF, 0.41 mmol) was slowly added and the reaction mixture was stirred at that temperature for 1 h. Then Pd(tBu3P)2 (7.0 mg, 0.03 mmol) was added, followed by 2-iodo-4-[(5-nitro-2-pyrimidinyl)oxy]benzonitrile (Intermediate 121, 50.0 mg) in THF (1.0 mL) and the reaction mixture was stirred at −15° C. for 1 h and then the NaCl/ice bath was removed. After 2 hours at r.t. additional 3.5 mg (0.015 mmol) of (tBu3P)2 were added. The reaction was quenched with NH4Cl (saturated aqueous solution) and extracted with EtOAc (three times). The collected organic were dried over Na2SO4, filtered and evaporated. The residue obtained was charged on a silica gel column and eluted with Cyclohexane/EtOAc (from 100:0 to 90:10 Cyclohexane/EtOAc, plateau at 90:10) affording 25 mg of the title compound.

Workup

  1. stirringthe reaction mixture was stirred at −15° C. for 1 h
  2. customthe NaCl/ice bath was removed
  3. customThe reaction was quenched with NH4Cl (saturated aqueous solution)
  4. extractionextracted with EtOAc (three times)
  5. dry with materialThe collected organic were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue obtained
  9. additionwas charged on a silica gel column
  10. washeluted with Cyclohexane/EtOAc (from 100:0 to 90:10 Cyclohexane/EtOAc, plateau at 90:10)

Sources & evidence

ORD record
ord-c0023cc7386f407cbf436bc680aa7984
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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