Sodium bis(trimethylsilyl)amide → N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,4-dimethylpiperazin-1-yl)benzamide

HRID 16765Notes

Reaction equation

HRID 16765 reaction equation
[CH3:1][CH:2]1[N:7]([CH3:8])[CH2:6][CH2:5][N:4]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=O)=[CH:11][CH:10]=2)[CH2:3]1.[NH2:19][C:20]1[N:24](C(OC(C)(C)C)=O)[N:23]=[C:22]([CH2:32][CH2:33][C:34]2[CH:39]=[C:38]([O:40][CH3:41])[CH:37]=[C:36]([O:42][CH3:43])[CH:35]=2)[CH:21]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH3:41][O:40][C:38]1[CH:39]=[C:34]([CH2:33][CH2:32][C:22]2[NH:23][N:24]=[C:20]([NH:19][C:13](=[O:15])[C:12]3[CH:11]=[CH:10][C:9]([N:4]4[CH2:5][CH2:6][N:7]([CH3:8])[CH:2]([CH3:1])[CH2:3]4)=[CH:18][CH:17]=3)[CH:21]=2)[CH:35]=[C:36]([O:42][CH3:43])[CH:37]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440403Methyl 4-(3,4-dimethylpiperazin-1-yl)benzoate

Product 1

HCID 66589815N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,4-dimethylpiperazin-1-yl)benzamideYield 19.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,4-dimethylpiperazin-1-yl)benzamide was prepared as for Example 94, but starting from methyl 4-(3,4-dimethylpiperazin-1-yl)benzoate (221 mg, 0.84 mmol), tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (244 mg, 0.7 mmol) and 1M NaHMDS (1.13 ml, 1.13 mmol) in THF (5 ml). The crude product was purified by reverse phase prep. HPLC (basic) using a 38-58% gradient of acetonitrile in water containing 1% 0.880 ammonium hydroxide. The clean fractions were taken and evaporated to afford the title compound as a white solid (63 mg, 19%); 1H NMR (500.13 MHz, DMSO-d6) δ 1.12 (3H, d), 1.89-1.90 (3H, m), 2.32 (3H, s), 2.35-2.40 (1H, m), 2.64-2.68 (1H, m), 2.86-2.91 (1H, m), 2.89 (4H, t), 3.00 (1H, s), 3.64-3.68 (2H, m), 3.74 (6H, s), 6.32 (1H, s), 6.33 (1H, t), 6.42 (2H, d), 6.94-6.96 (2H, m), 7.86-7.88 (2H, m). MS: m/z 464 (MH+).

Workup

  1. customN-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,4-dimethylpiperazin-1-yl)benzamide was prepared as for Example 94
  2. customThe crude product was purified by reverse phase prep
  3. customevaporated

Sources & evidence

ORD record
ord-ddbe14ce56824fabb3fcf6a1c730cd4c
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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