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

HRID 16741

Reaction equation

HRID 16741 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OC([N:18]1[C:22]([NH2:23])=[CH:21][C:20]([CH2:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=2)=[N:19]1)=O)(C)(C)C.[NH2:36][CH:37]([CH3:49])[CH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43](OC)=[O:44])=[CH:41][CH:40]=1>C1COCC1>[NH2:36][CH:37]([CH3:49])[CH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43]([NH:23][C:22]2[CH:21]=[C:20]([CH2:24][CH2:25][C:26]3[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=3)[NH:19][N:18]=2)=[O:44])=[CH:41][CH:40]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 15034329Methyl 4-(2-aminopropyl)benzoateHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

Product 1

HCID 665897674-(2-aminopropyl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]benzamideYield 4.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of NaHMDS in THF (1 M, 0.86 ml, 0.86 mmol, 1.5 eq) was added dropwise at ambient temperature to a mixture of tert-butyl-5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate (200 mg, 0.58 mmol, 1 eq) and methyl 4-(2-aminopropyl)benzoate (133 mg, 0.69 mmol, 1.2 eq) in THF (1 ml). The reaction mixture was stirred at ambient temperature for 2 h. It was then concentrated and the crude product was purified by reverse-phase prep. HPLC (basic) using a gradient of acetonitrile in water containing 1% ammonium hydroxide solution. The clean fractions were taken and evaporated to afford the title compound as a pale yellow gum (10 mg, 4% yield); 1H NMR (399.902 MHz, DMSO) δ 0.89 (3H, d), 2.53-2.47 (2H, m), 2.80 (4H, s), 3.01-2.93 (1H, m), 3.65 (6H, s), 6.25-6.24 (1H, m), 6.34 (2H, d), 6.40 (1H, s), 7.21 (2H, d), 7.84 (2H, d), 10.47 (1H, br.s), 12.06 (1H, br.s). MS: m/z 409 (MH+)

Workup

  1. concentrationIt was then concentrated
  2. customthe crude product was purified by reverse-phase prep
  3. customevaporated

Sources & evidence

ORD record
ord-aad9bcbf9c4543e196c736ec95b4a417
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Linked notes

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