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

HRID 1911348Notes

Reaction equation

HRID 1911348 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]3[CH:20]=[CH:19][C:13]([C:14]([O:16]CC)=O)=[CH:12][CH:11]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]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>[CH:1]1([N:4]2[CH2:5][CH2:6][N:7]([C:10]3[CH:11]=[CH:12][C:13]([C:14]([NH:21][C:22]4[CH:23]=[C:24]([CH2:34][CH2:35][C:36]5[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[C:38]([O:44][CH3:45])[CH:37]=5)[NH:25][N:26]=4)=[O:16])=[CH:19][CH:20]=3)[CH2:8][CH2:9]2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440407Ethyl 4-(4-cyclopropylpiperazin-1-yl)benzoate

Product 1

HCID 249622804-(4-cyclopropylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]benzamideYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-cyclopropylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]benzamide was prepared as for Example 94, but starting from ethyl 4-(4-cyclopropylpiperazin-1-yl)benzoate (193 mg, 0.7 mmol), tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (292 mg, 0.84 mmol) and 1M NaHMDS (1.23 ml, 1.23 mmol) in THF (5 ml). The crude product was purified by reverse phase prep. HPLC (acidic) using a 16-36% gradient of acetonitrile in water containing 0.1% TFA. The clean fractions were neutralised and evaporated to afford the title compound as a white solid (40 mg, 12%); 1H NMR (500.13 MHz, DMSO-d6+d4 Acetic Acid) δ 0.46 (2H, d), 0.50 (2H, d), 1.79-1.84 (1H, m), 2.78 (4H, t), 2.90 (4H, s), 3.24-3.31 (4H, m), 3.75 (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).

Workup

  1. custom4-(4-cyclopropylpiperazin-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. customevaporated

Sources & evidence

ORD record
ord-722d5324486a4bc2a32797b4c7bf7bf8
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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