Ammonium Chloride → N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide

HRID 16793

Reaktionsgleichung

Reaktionsgleichung von HRID 16793
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=O)=[CH:21][CH:20]=2)[CH2:14][CH2:13]1.[NH2:29][C:30]1[N:34](C(OC(C)(C)C)=O)[N:33]=[C:32]([CH2:42][CH2:43][C:44]2[CH:49]=[C:48]([O:50][CH3:51])[CH:47]=[C:46]([O:52][CH3:53])[CH:45]=2)[CH:31]=1.[NH4+].[Cl-]>C1COCC1.CC(N(C)C)=O>[CH3:51][O:50][C:48]1[CH:49]=[C:44]([CH2:43][CH2:42][C:32]2[NH:33][N:34]=[C:30]([NH:29][C:23](=[O:25])[C:22]3[CH:21]=[CH:20][C:19]([CH2:18][N:15]4[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17][CH2:16]4)=[CH:28][CH:27]=3)[CH:31]=2)[CH:45]=[C:46]([O:52][CH3:53])[CH:47]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 782222Methyl 4-((4-methylpiperazin-1-yl)methyl)benzoateHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

Produkt 1

HCID 66589825N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamideAusbeute 5,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

A solution of NaHMDS (1M in THF) (2.83 mL, 2.83 mmol) was added dropwise to a stirred solution of methyl 4-((4-methylpiperazin-1-yl)methyl)benzoate (0.351 g, 1.41 mmol) and tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (0.589 g, 1.70 mmol) in THF (3 mL), over a period of 10 mins under nitrogen. DMA (3 mL) was added. The resulting solution was stirred at room temperature for 60 h. A further aliquot of NaHMDS (1.415 mL, 1.415 mmol) was added dropwise and the solution was stirred at room temperature for a further 90 mins. The reaction mixture was poured into saturated NH4Cl (25 mL), extracted with EtOAc (2×25 mL), washed with saturated brine and dried over MgSO4, filtered and evaporated to afford the crude product (0.8776 g) as an orange gum. 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 (0.034 g, 5.19%) as a white solid; 1H NMR (500.0 MHz, DMSO-d6) δ 2.18 (3H, s), 2.34-2.37 (2H, m), 3.54 (2H, s), 3.73 (3H, s), 6.32-6.33 (1H, t), 6.41-6.42 (2H, d), 7.38-7.39 (1H, d), 7.90-7.92 (1H, d), 10.02 (1H, s), 11.79 (1H, s)

Aufarbeitung

  1. stirringthe solution was stirred at room temperature for a further 90 mins
  2. extractionextracted with EtOAc (2×25 mL)
  3. washwashed with saturated brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford the crude product (0.8776 g) as an orange gum
  8. customThe crude product was purified by preparative HPLC
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-98001c8d31304e21941cfe8de6cd2b42
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737149B2

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