Hydrochloric Acid → HCID 178489796, compound

HRID 1092106Notes

Reaction equation

HRID 1092106 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][C@H:24]1[N:29]([CH3:30])[C@@H:28]([CH3:31])[CH2:27][N:26]([C:32]2[N:37]=[CH:36][C:35]([C:38](OC)=[O:39])=[CH:34][N:33]=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:38]([C:35]3[CH:36]=[N:37][C:32]([N:26]4[CH2:27][C@H:28]([CH3:31])[N:29]([CH3:30])[C@H:24]([CH3:23])[CH2:25]4)=[N:33][CH:34]=3)=[O:39])[NH:20][N:21]=2)[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 66589963HCID 66589963, compoundHCID 178489815HCID 178489815, compound

Product 1

HCID 178489796HCID 178489796, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.04 ml, 2.08 mmol) was added dropwise to a suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (205 mg, 0.83 mmol) and methyl 2-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)pyrimidine-5-carboxylate (220 mg, 0.83 mmol) in toluene (5.257 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 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 (157 mg, 39%) 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 preparative HPLC
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-deb53fb299d24df8a18d7f19417282f5
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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