Nitrogen → HCID 71253142, compound

HRID 1427407Notes

Reaction equation

HRID 1427407 reaction equation
I[C:2]1[S:3][CH:4]=[C:5]([CH3:7])[CH:6]=1.[C:8]([C:12]1[CH:16]=[C:15]([NH2:17])[NH:14][N:13]=1)([CH3:11])([CH3:10])[CH3:9].CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+].N#N>C1(C)C=CC=CC=1.[Cu]I>[C:8]([C:12]1[CH:16]=[C:15]([NH2:17])[N:14]([C:2]2[S:3][CH:4]=[C:5]([CH3:7])[CH:6]=2)[N:13]=1)([CH3:11])([CH3:10])[CH3:9]

Participants

8

Reactant 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 232616792-Iodo-4-methylthiopheneHCID 178441179HCID 178441179, compound

Product 1

HCID 71253142HCID 71253142, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-iodo-4-methylthiophene (WO 2008/121666) (1.00 g, 4.50 mmol) in anhydrous toluene (15.0 mL) was added 3-tert-butyl-1H-pyrazol-5-amine (683 mg, 4.91 mmol) followed by (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (140 μL, 0.89 mmol) and potassium carbonate (1.30 g, 9.37 mmol). The mixture was purged with N2, copper(I) iodide (42 mg, 0.22 mmol) was added and the reaction mixture was heated at reflux under N2 for 16 hr during which time most of the solvent was lost. The resulting mixture was partitioned between ethyl acetate (150 mL) and water (150 mL) and the organic layer was separated and extracted with aq. citric acid solution (10% w/v, 150 mL) followed by brine (50 mL), and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 120 g, DCM, isocratic elution) to afford the title compound, Intermediate A14, as a brown solid (340 mg, 32%); Rt 1.94 min (Method 2); m/z 236 (M+H)+ (ES+).

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux under N2 for 16 hr during which time most of the solvent
  4. customThe resulting mixture was partitioned between ethyl acetate (150 mL) and water (150 mL)
  5. customthe organic layer was separated
  6. extractionextracted with aq. citric acid solution (10% w/v, 150 mL)
  7. customdried
  8. customevaporated in vacuo
  9. customThe residue was purified by flash column chromatography (SiO2, 120 g, DCM, isocratic elution)

Sources & evidence

ORD record
ord-e7908fa6b7624e97a25522a4e7627ec1
Source dataset
uspto-grants-2015_01
Patent number
US08933228B2

Reaction notes

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