Hydrochloric Acid → N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-5-piperazin-1-yl-thiophene-2-carboxamide

HRID 1911315Notes

Reaction equation

HRID 1911315 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:18][C:17]([C:19]([OH:21])=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)C.ClC(N(C)C)=C(C)C.[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.Cl.O1CCOCC1>C1COCC1.N1C=CC=CC=1>[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:19]([C:17]3[S:18][C:14]([N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[CH:15][CH:16]=3)=[O:21])[CH:32]=2)[CH:46]=[C:47]([O:53][CH3:54])[CH:48]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 543134535-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}thiophene-2-carboxylic acidHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

Product 1

HCID 66589690N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-5-piperazin-1-yl-thiophene-2-carboxamideYield 13.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]thiophene-2-carboxylic acid (150 mg, mmol) was dissolved in dry THF (10 ml) under nitrogen, 1-chloro-N,N,2-trimethyl-prop-1-en-1-amine (177 μl, mmol) was added and the mixture was stirred at room temperature for 3.5 h. Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate (167 mg, mmol) and pyridine (47 μl, mmol) were added and the reaction was heated to 65° C. for 18 h. The reaction mixture was then cooled to room temperature and 4M HCl in dioxane (2.0 ml, 2.0 mmol) added. The mixture was stirred overnight at room temperature, evaporated and the residue was purified by acidic prep. HPLC, eluting with a gradient of 24-32% MeCN in 0.1% TFA in water. The clean fractions were taken and evaporated to give the title compound as a pale green solid (28.7 mg, 11%); 1H NMR (399.902 MHz, DMSO) δ 2.79 (s, 4H), 3.21 (s, 4H), 3.34 (s, 4H), 3.64 (s, 6H), 6.29 (m, 5H), 7.77 (m, 1H), 8.71 (s, 1H), 10.37 (s, 1H) MS: m/z=442 (MH+)

Workup

  1. temperaturethe reaction was heated to 65° C. for 18 h
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. stirringThe mixture was stirred overnight at room temperature
  4. customevaporated
  5. customthe residue was purified by acidic prep
  6. washHPLC, eluting with a gradient of 24-32% MeCN in 0.1% TFA in water
  7. customevaporated

Sources & evidence

ORD record
ord-ec4ac94f56b7418bb98414c842dc2486
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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