Trimethylaluminum → HCID 178462711, compound

HRID 1911419Notes

Reaction equation

HRID 1911419 reaction equation
C[Al](C)C.[CH2:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[N:18]=[CH:17][C:16]([C:19]([O:21]C)=O)=[CH:15][N:14]=2)[CH2:9][CH:8]1[CH3:23])[CH3:6].[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:19]([C:16]3[CH:17]=[N:18][C:13]([N:10]4[CH2:11][CH2:12][N:7]([CH2:5][CH3:6])[CH:8]([CH3:23])[CH2:9]4)=[N:14][CH:15]=3)=[O:21])[NH:39][N:40]=2)[CH:27]=[C:26]([O:25][CH3:24])[CH:31]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589848Methyl 2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178462711HCID 178462711, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.65 ml, 3.31 mmol) was added dropwise to a stirred suspension of methyl 2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxylate (303 mg, 1.15 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (283 mg, 1.15 mmol) in toluene (5.73 ml) at room temperature. The resulting solution was stirred at 60° C. overnight. 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 as a yellow dry film. 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 (269 mg, 49%) as a cream 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 as a yellow dry film
  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-f9a8731fbeec4d14bf969c199395d7d5
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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