Hydrochloric Acid → HCID 178489808, compound

HRID 16836Notes

Reaction equation

HRID 16836 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.[CH3:23][CH:24]1[N:29]([CH3:30])[CH2:28][CH2:27][N:26]([C:31]2[N:36]=[CH:35][C:34]([C:37](OC)=[O:38])=[CH:33][N:32]=2)[CH2:25]1.Cl>C1(C)C=CC=CC=1.CO>[CH3:14][O:13][C:11]1[CH:10]=[C:9]([CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([NH:22][C:37]([C:34]3[CH:33]=[N:32][C:31]([N:26]4[CH2:27][CH2:28][N:29]([CH3:30])[CH:24]([CH3:23])[CH2:25]4)=[N:36][CH:35]=3)=[O:38])[NH:20][N:21]=2)[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 66589755HCID 66589755, compoundHCID 178489815HCID 178489815, compound

Product 1

HCID 178489808HCID 178489808, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.31 ml, 2.62 mmol) was added dropwise to a suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (260 mg, 1.05 mmol) and methyl 2-(3,4-dimethylpiperazin-1-yl)pyrimidine-5-carboxylate (263 mg, 1.05 mmol) in toluene (5.26 ml) at 25° C. The resulting solution was stirred at 60° C. for 18 h. The reaction mixture was poured into methanol (50 mL) and acidified with HCl (2M aqueous solution, to obtain a clear freely stirring 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 silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane. Fractions containing product were evaporated to dryness to give material that was still impure. The residue was repurified 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 (175 mg, 36%) as a white solid.

Workup

  1. customto obtain a clear freely stirring solution)
  2. customThe crude product was purified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. customevaporated to dryness
  5. customto afford impure product
  6. customThe impure material was purified by silica column chromatography
  7. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane
  8. additionFractions containing product
  9. customwere evaporated to dryness
  10. customto give material that
  11. customThe residue was repurified by preparative HPLC
  12. additionFractions containing the desired compound
  13. customwere evaporated to dryness

Sources & evidence

ORD record
ord-8a3ee030823141aa8d31f7feb24d3b1b
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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