Trimethylaluminum → HCID 178489780, compound

HRID 1911434Notes

Reaction equation

HRID 1911434 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][N:24]1[CH2:29][CH:28]=[C:27]([C:30]2[N:31]=[CH:32][C:33]([C:36](OC)=[O:37])=[N:34][CH:35]=2)[CH2:26][CH2:25]1>C1(C)C=CC=CC=1>[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:36]([C:33]3[CH:32]=[N:31][C:30]([C:27]4[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH:26]=4)=[CH:35][N:34]=3)=[O:37])[NH:20][N:21]=2)[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589840methyl 5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489780HCID 178489780, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.74 ml, 3.48 mmol) was added dropwise to a stirred suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (343 mg, 1.39 mmol) and methyl 5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate (324 mg, 1.39 mmol) in anhydrous toluene (6.94 ml) at ambient temperature. The resulting solution was then stirred at 60° C. for 18 h. The reaction mixture was quenched into methanol (100 mL) and treated with HCl (2M aqueous solution, to pH7 or lower) and purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and 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 (152 mg, 24%) as a white solid.

Workup

  1. customThe reaction mixture was quenched into methanol (100 mL)
  2. additiontreated with HCl (2M aqueous solution, to pH7 or lower)
  3. custompurified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customevaporated 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-96415e8b2a0e44e08ee552bc5ad9a777
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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