Potassium sodium tartarate → N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxamide

HRID 16842Notes

Reaction equation

HRID 16842 reaction equation
C[Al](C)C.[CH3:5][C:6]1([CH3:22])[NH:11][CH2:10][CH2:9][N:8]([C:12]2[S:16][C:15]([C:17]([O:19]CC)=O)=[CH:14][CH:13]=2)[CH2:7]1.Cl.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH2:34][O: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.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH3:33][O:32][C:30]1[CH:29]=[C:28]([CH2:34][O:35][C:36]2[CH:37]=[C:38]([NH:41][C:17]([C:15]3[S:16][C:12]([N:8]4[CH2:9][CH2:10][NH:11][C:6]([CH3:5])([CH3:22])[CH2:7]4)=[CH:13][CH:14]=3)=[O:19])[NH:39][N:40]=2)[CH:27]=[C:26]([O:25][CH3:24])[CH:31]=1

Participants

8

Reactant 4

HCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 574403805-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochlorideHCID 66589679HCID 66589679, compound

Product 1

HCID 66589889N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxamideYield 15.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred solution of ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.268 g, 1 mmol) and 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochloride (0.286 g, 1.00 mmol) in toluene (7.14 ml) at 65° C. under nitrogen. The reaction mixture was stirred and heated at 65° C. for 4 h then 50° C. for 18 h followed by 80° C. for 5 h. Ethyl acetate (5 mL) was added to the reaction mixture followed by a solution of potassium sodium tartrate (5 mL, 20% aqueous). More ethyl acetate (50 mL) and water (25 mL) was added and the mixture was filtered through celite. The filtrate was transferred to a separating funnel and the aqueous layer removed. The ethyl acetate layer was washed with saturated brine and then dried over magnesium sulphate. After filtration the solvent was evaporated to give the crude product as a yellow gum. The crude product was purified by preparative LCMS, 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 (0.073 g, 15.48%) as a white solid.

Workup

  1. filtrationthe mixture was filtered through celite
  2. customThe filtrate was transferred to a separating funnel
  3. customthe aqueous layer removed
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationAfter filtration the solvent
  7. customwas evaporated
  8. customto give the crude product as a yellow gum
  9. customThe crude product was purified by preparative LCMS
  10. additionFractions containing the desired compound
  11. customwere evaporated to dryness

Sources & evidence

ORD record
ord-fc3dbbd8a23444f3b8066829388d5400
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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