Potassium sodium tartarate → N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(4-methylpiperazin-1-yl)thiophene-2-carboxamide

HRID 1911383노트

반응식

HRID 1911383 반응식
C[Al](C)C.[CH3:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:16][C:15]([C:17]([O:19]CC)=O)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.Cl.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH2:33][O: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.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH3:32][O:31][C:29]1[CH:28]=[C:27]([CH2:33][O:34][C:35]2[CH:36]=[C:37]([NH:40][C:17]([C:15]3[S:16][C:12]([N:9]4[CH2:8][CH2:7][N:6]([CH3:5])[CH2:11][CH2:10]4)=[CH:13][CH:14]=3)=[O:19])[NH:38][N:39]=2)[CH:26]=[C:25]([O:24][CH3:23])[CH:30]=1

참가 물질

8

반응물 4

HCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 574403805-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochlorideHCID 57440415Ethyl 5-(4-methylpiperazin-1-yl)thiophene-2-carboxylate

생성물 1

HCID 66589833N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(4-methylpiperazin-1-yl)thiophene-2-carboxamide수율 32.1%

시약·촉매·용매 3

HCID 962Water용매HCID 1140Toluene용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred solution of ethyl 5-(4-methylpiperazin-1-yl)thiophene-2-carboxylate (0.254 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 20° C. under nitrogen. The reaction mixture was stirred at room temperature for 18 h and then heated at 65° C. for 6 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 solid. 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 (0.147 g, 32.1%) as a white solid.

후처리

  1. temperatureheated at 65° C. for 6 h
  2. filtrationthe mixture was filtered through celite
  3. customThe filtrate was transferred to a separating funnel
  4. customthe aqueous layer removed
  5. washThe ethyl acetate layer was washed with saturated brine
  6. dry with materialdried over magnesium sulphate
  7. filtrationAfter filtration the solvent
  8. customwas evaporated
  9. customto give the crude product as a yellow solid
  10. customThe crude product was purified by preparative HPLC
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-1375aa69a12247738c28ac0b55a62a28
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08604022B2

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