Sodium bis(trimethylsilyl)amide → HCID 66589725, compound

HRID 1911351Notes

Reaction equation

HRID 1911351 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:21]=[CH:20][C:14]([C:15](OCC)=[O:16])=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[NH2:22][C:23]1[N:27](C(OC(C)(C)C)=O)[N:26]=[C:25]([CH2:35][CH2:36][C:37]2[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[C:39]([O:45][CH3:46])[CH:38]=2)[CH:24]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11]3[CH:21]=[CH:20][C:14]([C:15]([NH:22][C:23]4[CH:24]=[C:25]([CH2:35][CH2:36][C:37]5[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[C:39]([O:45][CH3:46])[CH:38]=5)[NH:26][N:27]=4)=[O:16])=[CH:13][CH:12]=3)[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440408Ethyl 4-(4-cyclobutylpiperazin-1-yl)benzoate

Product 1

HCID 66589725HCID 66589725, compoundYield 6.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-cyclobutylpiperazin-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-cyclobutylpiperazin-1-yl)benzoate (202 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 (basic) using a 39-59% gradient of acetonitrile in water containing 1% 0.880 ammonia. The clean fractions were combined and evaporated to afford the title compound (21 mg, 6%); 1H NMR (399.9 MHz, DMSO-d6) δ 1.61-1.71 (2H, m), 1.81-1.86 (2H, m), 1.99-2.02 (2H, m), 2.38 (4H, t), 2.75 (1H, s), 2.85-2.87 (4H, m), 3.26-3.27 (4H, m), 3.72 (6H, d), 6.33 (1H, t), 6.42-6.43 (2H, m), 6.45 (1H, s), 6.95 (2H, d), 7.90 (2H, d), 10.29 (1H, s), 12.07 (1H, s). MS=m/z 490 (MH+).

Workup

  1. custom4-(4-cyclobutylpiperazin-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-d291ced3582d4c588c671db1dfc42d84
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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