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

HRID 16793

Reaction equation

HRID 16793 reaction equation
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

Participants

7

Reactant 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

Product 1

HCID 66589825N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamideYield 5.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-98001c8d31304e21941cfe8de6cd2b42
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Linked notes

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