Trimethylaluminum → HCID 178489811, compound

HRID 16852Notes

Reaction equation

HRID 16852 reaction equation
C[Al](C)C.[CH3:5][CH:6]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[N:19]=[CH:18][C:17]([C:20]([O:22]C)=O)=[CH:16][N:15]=2)[CH2:9]1)[CH3:7].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([NH2:41])[NH:39][N:40]=2)[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1>C1(C)C=CC=CC=1>[CH3:33][O:32][C:30]1[CH:29]=[C:28]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([NH:41][C:20]([C:17]3[CH:18]=[N:19][C:14]([N:10]4[CH2:11][CH2:12][NH:13][C@@H:8]([CH:6]([CH3:5])[CH3:7])[CH2:9]4)=[N:15][CH:16]=3)=[O:22])[NH:39][N:40]=2)[CH:27]=[C:26]([O:25][CH3:24])[CH:31]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589787HCID 66589787, compoundHCID 178489815HCID 178489815, compound

Product 1

HCID 178489811HCID 178489811, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.23 mL, 2.46 mmol) was added dropwise to a stirred suspension of (S)-methyl 2-(3-propan-2-ylpiperazin-1-yl)pyrimidine-5-carboxylate (260 mg, 0.98 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (243 mg, 0.98 mmol) in toluene (8.38 mL) at room temperature. The reaction was then stirred at 60° C. for 18 h under a nitrogen atmosphere. The reaction mixture was quenched into methanol (100 mL) and treated with HCl (2N aqueous solution, until the pH was 7 or lower). The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford impure product. The crude product was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (292 mg, 62%) as a white solid.

Workup

  1. customThe reaction mixture was quenched into methanol (100 mL)
  2. additiontreated with HCl (2N aqueous solution
  3. customThe crude product was purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customwere evaporated to dryness
  6. customto afford impure product
  7. customThe crude product was purified by preparative HPLC
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b142c9ead1ba4650a4652a0bfae58ed5
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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