Trimethylaluminum → HCID 178489754, compound

HRID 1092069Notes

Reaction equation

HRID 1092069 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][CH:7]([C:10]3[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=O)=[CH:12][CH:11]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH2:30][CH2:31][C:32]2[CH:33]=[C:34]([NH2:37])[NH:35][N:36]=2)[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=1.C[Al](C)C>C1(C)C=CC=CC=1>[CH:1]1([N:4]2[CH2:5][CH2:6][CH:7]([C:10]3[CH:11]=[CH:12][C:13]([C:14]([NH:37][C:34]4[NH:35][N:36]=[C:32]([CH2:31][CH2:30][C:24]5[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=[C:22]([O:21][CH3:20])[CH:23]=5)[CH:33]=4)=[O:16])=[CH:18][CH:19]=3)[CH2:8][CH2:9]2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 57440413Methyl 4-(1-cyclopropylpiperidin-4-yl)benzoateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489754HCID 178489754, compoundYield 35.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

Methyl 4-(1-cyclopropylpiperidin-4-yl)benzoate (0.259 g, 1 mmol), 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.247 g, 1.00 mmol) in toluene (10 ml) was treated with a 2M solution of trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, under nitrogen. The reaction mixture was heated at 60° C. for 18 h. The reaction mixture was cooled and the reaction quenched with methanol (40 ml) and acidified with 2N HCl (1 ml). The crude reaction mixture was purified by ion exchange chromatography, using an SCX column. The crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% 2.5M ammonia/methanol in DCM. Pure fractions were evaporated to dryness and the product crystallised from DCM/diethyl ether to give the title compound (0.170 g, 35.8%) as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe reaction quenched with methanol (40 ml)
  3. customThe crude reaction mixture
  4. customwas purified by ion exchange chromatography
  5. washThe crude product was eluted from the column
  6. customwere evaporated to dryness
  7. customThe crude product was purified by silica column chromatography
  8. washeluting with a gradient of 0 to 5% 2.5M ammonia/methanol in DCM
  9. customPure fractions were evaporated to dryness
  10. customthe product crystallised from DCM/diethyl ether

Sources & evidence

ORD record
ord-889589ca64bf40f5af8ba8793f92198c
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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