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

HRID 16743

反応式

HRID 16743 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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+)

後処理

  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

出典と根拠

ORDレコード
ord-e0fc0167b5fc4fde8ce6d5a01db439a0
出典データセット
uspto-grants-2010_06
特許番号
US07737149B2

関連ノート

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