Trimethylaluminum → HCID 178462583, compound

HRID 16896Notes

Reaction equation

HRID 16896 reaction equation
C[Al](C)C.[CH2:5]([N:7]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[N:19]=[CH:18][C:17]([C:20]([O:22]C)=O)=[CH:16][N:15]=2)[CH2:9][CH2:8]1)[CH3:6].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([NH2:41])[NH:39][N:40]=2)[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1>C1(C)C=CC=CC=1>[CH3:33][O:32][C:30]1[CH:29]=[C:28]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([NH:41][C:20]([C:17]3[CH:18]=[N:19][C:14]([N:10]4[CH2:11][CH2:12][CH2:13][N:7]([CH2:5][CH3:6])[CH2:8][CH2:9]4)=[N:15][CH:16]=3)=[O:22])[NH:39][N:40]=2)[CH:27]=[C:26]([O:25][CH3:24])[CH:31]=1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 66589959Methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178462583HCID 178462583, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (1.25 ml, 2.50 mmol) was added dropwise to a stirred suspension of methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (265 mg, 1.00 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (248 mg, 1.00 mmol) in toluene (5.01 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 desired product still contained an impurity, so they were concentrated to dryness and purified by crystallisation from MeCN to afford the title compound (104 mg, 22%) 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 desired product
  10. concentrationso they were concentrated to dryness
  11. custompurified by crystallisation from MeCN

Sources & evidence

ORD record
ord-ce6c53beef6b4f5984c115f44f322d35
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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