Ammonium Chloride → N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(4-methylpiperazine-1-carbonyl)benzamide

HRID 1911344Notes

Reaction equation

HRID 1911344 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26]C)=O)=[CH:22][CH:21]=2)=[O:19])[CH2:14][CH2:13]1.[NH2:30][C:31]1[N:35](C(OC(C)(C)C)=O)[N:34]=[C:33]([CH2:43][CH2:44][C:45]2[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]([O:53][CH3:54])[CH:46]=2)[CH:32]=1.[NH4+].[Cl-]>C1COCC1>[CH3:52][O:51][C:49]1[CH:50]=[C:45]([CH2:44][CH2:43][C:33]2[NH:34][N:35]=[C:31]([NH:30][C:24](=[O:26])[C:23]3[CH:22]=[CH:21][C:20]([C:18]([N:15]4[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17][CH2:16]4)=[O:19])=[CH:29][CH:28]=3)[CH:32]=2)[CH:46]=[C:47]([O:53][CH3:54])[CH:48]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 17178223Methyl 4-(4-methylpiperazine-1-carbonyl)benzoateHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

Product 1

HCID 66589687N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(4-methylpiperazine-1-carbonyl)benzamideYield 56.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of NaHMDS (1M in THF) (2.86 mL, 2.86 mmol) was added dropwise to a stirred solution of methyl 4-(4-methylpiperazine-1-carbonyl)benzoate (0.250 g, 0.95 mmol) and tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (0.397 g, 1.14 mmol) in THF (2 mL), over a period of 10 mins under nitrogen. The resulting solution was stirred at room temperature for 18 h. The reaction mixture was poured into saturated NH4Cl (25 mL), extracted with EtOAc (2×25 mL), washed with saturated brine and dried over MgSO4, filtered and evaporated to afford the crude product (0.501 g) as a yellow gum. The crude product was purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% ammonium hydroxide) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (0.257 g, 56.5%) as a yellow solid; 1H NMR (399.9 MHz, DMSO-d6) δ 2.21 (3H, s), 2.25-2.40 (4H, m), 2.89 (4H, s), 3.16-3.20 (1H, d), 3.32 (4H, s), 3.72 (6H, d), 6.33 (1H, m), 6.42-6.44 (2H, d), 7.46-7.50 (2H, d), 8.02-8.06 (2H, d)

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. washwashed with saturated brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford the crude product (0.501 g) as a yellow gum
  7. customThe crude product was purified by preparative HPLC
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-f625e854e7f64c44b7e27c2b000788e6
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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