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

HRID 1911355

Reaction equation

HRID 1911355 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=O)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[NH2:20][C:21]1[N:25](C(OC(C)(C)C)=O)[N:24]=[C:23]([CH2:33][CH2:34][C:35]2[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[C:37]([O:43][CH3:44])[CH:36]=2)[CH:22]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[C:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:11]=[CH:12][C:13]([C:14]([NH:20][C:21]3[CH:22]=[C:23]([CH2:33][CH2:34][C:35]4[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[C:37]([O:43][CH3:44])[CH:36]=4)[NH:24][N:25]=3)=[O:16])=[CH:18][CH:19]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440409Methyl 4-(4-acetylpiperazin-1-yl)benzoate

Product 1

HCID 665897824-(4-acetylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]benzamideYield 1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-acetylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]benzamide was prepared as for Example 94, but starting from methyl 4-(4-acetylpiperazin-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 31-51% gradient of acetonitrile in water, containing 1% 0.880 ammonia. The clean fractions were taken and evaporated to afford the title compound as a white solid (3 mg, 1.0%); 1H NMR (399.9 MHz, DMSO-d6) δ 2.06 (3H, s), 2.78 (4H, s), 3.28 (2H, s) 3.25 (2H, t), 3.49-3.56 (4H, m), 3.73 (6H, s), 6.33 (1H, t), 6.42 (2H, d), 6.45 (1H, s), 6.99 (2H, d), 7.92 (2H, d), 10.32 (1H, s), 12.08 (1H, s).

Workup

  1. custom4-(4-acetylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]benzamide was prepared as for Example 94
  2. customThe crude product was purified by reverse phase prep
  3. additioncontaining 1% 0.880 ammonia
  4. customevaporated

Sources & evidence

ORD record
ord-b6b45187be0e435d873c0bcbbcc9ba43
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Linked notes

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