Trimethylaluminum → HCID 178489788, compound

HRID 16905Notes

Reaction equation

HRID 16905 reaction equation
C[Al](C)C.[CH3:5][N:6]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:18]=[CH:17][C:16]([C:19]([O:21]C)=O)=[CH:15][N:14]=2)[CH2:8][CH2:7]1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH2:33][CH2:34][C:35]2[CH:36]=[C:37]([NH2:40])[NH:38][N:39]=2)[CH:28]=[C:29]([O:31][CH3:32])[CH:30]=1>C1(C)C=CC=CC=1>[CH3:32][O:31][C:29]1[CH:28]=[C:27]([CH2:33][CH2:34][C:35]2[CH:36]=[C:37]([NH:40][C:19]([C:16]3[CH:17]=[N:18][C:13]([N:9]4[CH2:10][CH2:11][CH2:12][N:6]([CH3:5])[CH2:7][CH2:8]4)=[N:14][CH:15]=3)=[O:21])[NH:38][N:39]=2)[CH:26]=[C:25]([O:24][CH3:23])[CH:30]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589654Methyl 2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489788HCID 178489788, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (1.35 ml, 2.70 mmol) was added dropwise to a stirred suspension of methyl 2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (270 mg, 1.08 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (267 mg, 1.08 mmol) in toluene (5.39 ml) at 25° C. The resulting solution was stirred at 60° C. for 18 h. The cooled reaction mixture was quenched into methanol (50 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 pure desired compound were evaporated to dryness to afford the title compound (136 mg, 27%) as a cream solid. The fractions containing impure product were concentrated and purified by crystallisation from MeCN to afford the title compound (56.0 mg, 11%) as a beige solid.

Workup

  1. customThe cooled reaction mixture
  2. customwas quenched into methanol (50 mL)
  3. additiontreated with HCl (2M aqueous solution, to pH7 or lower)
  4. custompurified by ion exchange chromatography
  5. washThe desired product was eluted from the column
  6. customevaporated to dryness
  7. customto afford impure product
  8. customThe crude product was purified by preparative HPLC
  9. additionFractions containing pure desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b1e327e3ba0042298f95882c521be10f
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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