Trimethylaluminum → HCID 178489767, compound

HRID 16863Notes

Reaction equation

HRID 16863 reaction equation
C[Al](C)C.[CH3:5][C@H:6]1[N:11]([CH3:12])[C@@H:10]([CH3:13])[CH2:9][N:8]([C:14]2[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=O)=[CH:16][CH:15]=2)[CH2:7]1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH2:35][CH2:36][C:37]2[CH:38]=[C:39]([NH2:42])[NH:40][N:41]=2)[CH:30]=[C:31]([O:33][CH3:34])[CH:32]=1>C1(C)C=CC=CC=1>[CH3:34][O:33][C:31]1[CH:30]=[C:29]([CH2:35][CH2:36][C:37]2[CH:38]=[C:39]([NH:42][C:18](=[O:20])[C:17]3[CH:16]=[CH:15][C:14]([N:8]4[CH2:9][C@H:10]([CH3:13])[N:11]([CH3:12])[C@H:6]([CH3:5])[CH2:7]4)=[CH:24][CH:23]=3)[NH:40][N:41]=2)[CH:28]=[C:27]([O:26][CH3:25])[CH:32]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 57440416ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489767HCID 178489767, compoundYield 33.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

A 2M solution of trimethylaluminium (2.500 mL, 5.00 mmol) in toluene, was added dropwise to a stirred suspension of ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate (0.643 g, 2 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.495 g, 2.00 mmol) in toluene (10 mL) at room temperature. The solution was then heated at 60° C. for 18 h. The reaction mixture was cooled and quenched with methanol (15 ml) and 2N hydrochloric acid (5 ml). The crude reaction mixture was purified by ion exchange chromatography on a SCX column, eluting with 7N ammonia in methanol. The appropriate fractions were evaporated to give an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford, on crystallisation from DCM/diethyl ether, the title compound (0.322 g, 33.7%) as a cream solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with methanol (15 ml) and 2N hydrochloric acid (5 ml)
  3. customThe crude reaction mixture
  4. customwas purified by ion exchange chromatography on a SCX column
  5. washeluting with 7N ammonia in methanol
  6. customThe appropriate fractions were evaporated
  7. customto give an oil
  8. customThe crude product was purified by silica column chromatography
  9. washeluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM
  10. customPure fractions were evaporated to dryness
  11. customto afford, on crystallisation from DCM/diethyl ether

Sources & evidence

ORD record
ord-04ef702d9aa349aa9a295d641b6c2474
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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