Trimethylaluminum → HCID 178489792, compound

HRID 16900Notes

Reaction equation

HRID 16900 reaction equation
C[Al](C)C.[CH3:5][CH:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[CH:19][C:18]([C:21]([O:23]C)=O)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)[CH3:7].[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH2:35][CH2:36][C:37]2[CH:38]=[C:39]([NH2:42])[NH:40][N:41]=2)[CH:30]=[C:31]([O:33][CH3:34])[CH:32]=1>C1(C)C=CC=CC=1>[CH3:34][O:33][C:31]1[CH:30]=[C:29]([CH2:35][CH2:36][C:37]2[CH:38]=[C:39]([NH:42][C:21]([C:18]3[CH:19]=[N:20][C:15]([N:11]4[CH2:12][CH2:13][CH2:14][N:8]([CH:6]([CH3:5])[CH3:7])[CH2:9][CH2:10]4)=[N:16][CH:17]=3)=[O:23])[NH:40][N:41]=2)[CH:28]=[C:27]([O:26][CH3:25])[CH:32]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589803Methyl 2-(4-propan-2-yl-1,4-diazepan-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178489792HCID 178489792, compoundYield 17.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (1.19 ml, 2.38 mmol) was added dropwise to a stirred suspension of methyl 2-(4-propan-2-yl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (265 mg, 0.95 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (235 mg, 0.95 mmol) in toluene (4.76 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 an 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 the desired compound were evaporated to dryness to afford the title compound (81 mg, 17%) as a cream 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 the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-3e7aaa97cc7744f284c310bdf642bfac
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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