Hydrochloric Acid → HCID 178494581, compound

HRID 16871Notes

Reaction equation

HRID 16871 reaction equation
C[Al](C)C.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([NH2:22])[NH:20][N:21]=2)[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1.[CH3:23][O:24][CH2:25][CH:26]1[NH:31][CH2:30][CH2:29][N:28]([C:32]2[N:37]=[CH:36][C:35]([C:38](OC)=[O:39])=[CH:34][N:33]=2)[CH2:27]1.Cl>C1(C)C=CC=CC=1.CO>[CH3:14][O:13][C:11]1[CH:10]=[C:9]([CH2:15][CH2:16][C:17]2[CH:18]=[C:19]([NH:22][C:38]([C:35]3[CH:34]=[N:33][C:32]([N:28]4[CH2:29][CH2:30][NH:31][CH:26]([CH2:25][O:24][CH3:23])[CH2:27]4)=[N:37][CH:36]=3)=[O:39])[NH:20][N:21]=2)[CH:8]=[C:7]([O:6][CH3:5])[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 66589940Methyl 2-(3-(methoxymethyl)piperazin-1-yl)pyrimidine-5-carboxylateHCID 178489815HCID 178489815, compound

Product 1

HCID 178494581HCID 178494581, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trimethylaluminium (2M in toluene, 1.596 mL, 3.19 mmol) was added dropwise to a solution of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (314 mg, 1.27 mmol) and methyl 2-(3-(methoxymethyl)piperazin-1-yl)pyrimidine-5-carboxylate (338 mg, 1.27 mmol) in toluene (6.35 mL) at 25° C. The resulting mixture was stirred at 60° C. for 18 h under nitrogen. The reaction mixture was added to methanol (100 mL) and treated with HCl (2N aqueous solution, until pH was 7 or lower). 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 the crude product as a yellow dry film. 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 (348 mg, 57%) as a white solid.

Workup

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customwere evaporated to dryness
  4. customto afford the crude product as a yellow dry film
  5. customThe crude product was purified by preparative HPLC
  6. additionFractions containing the desired compound
  7. customwere evaporated to dryness

Sources & evidence

ORD record
ord-207afbc29312472ebaa9667cf690a3c2
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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