Trimethylaluminum → 2-(4-cyclopropylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrimidine-5-carboxamide

HRID 1911402Notes

Reaction equation

HRID 1911402 reaction equation
C[Al](C)C.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([NH2:22])[NH:20][N:21]=2)[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1.[CH:23]1([N:26]2[CH2:31][CH2:30][N:29]([C:32]3[N:37]=[CH:36][C:35]([C:38](OC)=[O:39])=[CH:34][N:33]=3)[CH2:28][CH2:27]2)[CH2:25][CH2:24]1>C1(C)C=CC=CC=1>[CH:23]1([N:26]2[CH2:27][CH2:28][N:29]([C:32]3[N:37]=[CH:36][C:35]([C:38]([NH:22][C:19]4[NH:20][N:21]=[C:17]([CH2:16][CH2:15][C:9]5[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=5)[CH:18]=4)=[O:39])=[CH:34][N:33]=3)[CH2:30][CH2:31]2)[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589828Methyl 2-(4-cyclopropylpiperazin-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 1784898042-(4-cyclopropylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrimidine-5-carboxamideYield 14%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminium (2M in toluene, 1.92 mL, 3.85 mmol) was added dropwise to a stirred suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (381 mg, 1.54 mmol) and methyl 2-(4-cyclopropylpiperazin-1-yl)pyrimidine-5-carboxylate (404 mg, 1.54 mmol) in toluene (7.7 mL) at 25° C. The resulting solution was stirred at ambient temperature for 18 h and then heated at 60° C. for 2 h. The reaction mixture was quenched with methanol (20 mL) and treated with HCl (2N aqueous solution). The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford impure product. The impure material was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (100 mg, 14%) as a solid.

Workup

  1. temperatureheated at 60° C. for 2 h
  2. customThe reaction mixture was quenched with methanol (20 mL)
  3. additiontreated with HCl (2N aqueous solution)
  4. customThe crude product was purified by ion exchange chromatography
  5. washThe desired product was eluted from the column
  6. customevaporated to dryness
  7. customto afford impure product
  8. customThe impure material was purified by preparative HPLC
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-56403f0ec63c4dfc8fe2240800f5ab05
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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