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

HRID 16795Notes

Reaction equation

HRID 16795 reaction equation
[CH3:1][CH:2]1[N:7]([CH3:8])[CH:6]([CH3:9])[CH2:5][N:4]([C:10]2[CH:20]=[CH:19][C:13]([C:14]([O:16]CC)=O)=[CH:12][CH:11]=2)[CH2:3]1.[NH2:21][C:22]1[N:26](C(OC(C)(C)C)=O)[N:25]=[C:24]([CH2:34][CH2:35][C:36]2[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[C:38]([O:44][CH3:45])[CH:37]=2)[CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH3:43][O:42][C:40]1[CH:41]=[C:36]([CH2:35][CH2:34][C:24]2[NH:25][N:26]=[C:22]([NH:21][C:14](=[O:16])[C:13]3[CH:12]=[CH:11][C:10]([N:4]4[CH2:5][CH:6]([CH3:9])[N:7]([CH3:8])[CH:2]([CH3:1])[CH2:3]4)=[CH:20][CH:19]=3)[CH:23]=2)[CH:37]=[C:38]([O:44][CH3:45])[CH:39]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440411Ethyl 4-(3,4,5-trimethylpiperazin-1-yl)benzoate

Product 1

HCID 66589637N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,4,5-trimethylpiperazin-1-yl)benzamideYield 7.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,4,5- trimethylpiperazin-1-yl)benzamide was prepared following the procedure as for Example 94, but starting from ethyl 4-(3,4,5-trimethylpiperazin-1-yl)benzoate (310 mg, 0.86 mmol), tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (225 mg, 0.65 mmol) and 1M NaHMDS (2.59 ml, 2.59 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 ammonia. The clean fractions were taken and evaporated to afford the title compound as a white solid (23 mg, 5.6%);1H NMR (399.99 MHz, CDCl3) δ1.09 (6H, d), 2.17-2.28 (2H, m), 2.22 (3H, s), 2.56 (2H, t), 2.81-2.90 (4H, m), 3.48 (2H, d), 3.68 (6H, s), 6.22 (1H, t), 6.28 (2H, s), 6.56 (1H, s), 6.78 (2H, d), 7.68 (2H, d0, 8.86 (1H, s), 9.65 (1H, s). MS: m/z 464 (MH+).

Workup

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

Sources & evidence

ORD record
ord-abe63c11e3ed4c8b93b0b0a5a37a9a4c
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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