Trimethylaluminum → HCID 178489800, compound

HRID 16832Notes

Reaction equation

HRID 16832 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.[CH2:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][N:27]2[CH2:26][CH2:25][N:24]1[C:32]1[N:37]=[CH:36][C:35]([C:38](OC)=[O:39])=[CH:34][N:33]=1>C1(C)C=CC=CC=1>[CH2:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][N:27]2[CH2:26][CH2:25][N:24]1[C:32]1[N:37]=[CH:36][C:35]([C:38]([NH:22][C:19]2[NH:20][N:21]=[C:17]([CH2:16][CH2:15][C:9]3[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=3)[CH:18]=2)=[O:39])=[CH:34][N:33]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589841methyl 2-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489800HCID 178489800, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminium (2M in toluene, 2.55 ml, 5.10 mmol) was added dropwise to a stirred suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (504 mg, 2.04 mmol) and methyl 2-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylate (535 mg, 2.04 mmol) in toluene (10.20 ml) at 25° C. The resulting solution was stirred at ambient temperature for 18 h and then at 60° C. for 2 h. The reaction mixture was quenched with methanol (20 mL) and treated with HCl (2N aqueous solution, until a freely stirred solution was obtained). 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 (288 mg, 30%) as a solid.

Workup

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

Sources & evidence

ORD record
ord-2c1f184e3dab49cf887a8abbcc92d3a7
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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