Trimethylaluminum → HCID 178489802, compound

HRID 1911403Notes

Reaction equation

HRID 1911403 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][CH2:32][N:27]2[CH2:26][CH2:25][N:24]1[C:33]1[N:38]=[CH:37][C:36]([C:39](OC)=[O:40])=[CH:35][N:34]=1>C1(C)C=CC=CC=1>[CH2:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][N:27]2[CH2:26][CH2:25][N:24]1[C:33]1[N:38]=[CH:37][C:36]([C:39]([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:40])=[CH:35][N:34]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589987Methyl 2-(1,3,4,6,7,8,9,9a-octahydropyrido[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489802HCID 178489802, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminium (2M in toluene, 1.45 mL, 2.90 mmol) was added dropwise to a stirred suspension of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (286 mg, 1.16 mmol) and methyl 2-(1,3,4,6,7,8,9,9a-octahydropyrido[2,1-c]pyrazin-2-yl)pyrimidine-5-carboxylate (320 mg, 1.16 mmol) in toluene (5.8 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 (238 mg, 42%) 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-1ad90328a974401c94dca923af79897e
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

Loading…