Trimethylaluminum → HCID 178489763, compound

HRID 1911417Notes

Reaction equation

HRID 1911417 reaction equation
[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[S:13][C:12]([C:14]([O:16]CC)=O)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH2:29][CH2:30][C:31]2[CH:32]=[C:33]([NH2:36])[NH:34][N:35]=2)[CH:24]=[C:25]([O:27][CH3:28])[CH:26]=1.C[Al](C)C>C1(C)C=CC=CC=1>[CH3:28][O:27][C:25]1[CH:24]=[C:23]([CH2:29][CH2:30][C:31]2[CH:32]=[C:33]([NH:36][C:14]([C:12]3[S:13][C:9]([N:5]4[CH2:6][CH2:7][CH2:8][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:10][CH:11]=3)=[O:16])[NH:34][N:35]=2)[CH:22]=[C:21]([O:20][CH3:19])[CH:26]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589793Ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489763HCID 178489763, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

Ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylate (0.201 g, 0.75 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.185 g, 0.75 mmol) in toluene (10 mL) were stirred at 20° C. and a 2M solution of trimethylaluminium in toluene (0.938 mL, 1.88 mmol) was added drop-wise. The reaction stirred under nitrogen at 60° C. for 18 h. The reaction mixture was cooled and quenched by pouring into methanol (50 ml), acidified with few drops of 2N hydrochloric acid. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude 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 (0.162 g, 46.0%) as a tan solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched
  3. additionby pouring into methanol (50 ml)
  4. customThe crude product was purified by ion exchange chromatography
  5. washThe desired product was eluted from the column
  6. customwere evaporated to dryness
  7. customto afford crude product
  8. customThe crude product was purified by preparative HPLC
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b93646a8659b4d6dbf6c55f643bdbdda
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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