Pyridine → N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-3-methoxy-benzamide

HRID 16738

反応式

HRID 16738 の反応式
ClC(N(C)C)=C(C)C.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O.[NH2:20][C:21]1[N:25](C(OC(C)(C)C)=O)[N:24]=[C:23]([CH2:33][CH2:34][C:35]2[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[C:37]([O:43][CH3:44])[CH:36]=2)[CH:22]=1.N1C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:42][O:41][C:39]1[CH:40]=[C:35]([CH2:34][CH2:33][C:23]2[NH:24][N:25]=[C:21]([NH:20][C:14](=[O:16])[C:13]3[CH:17]=[CH:18][CH:19]=[C:11]([O:10][CH3:9])[CH:12]=3)[CH:22]=2)[CH:36]=[C:37]([O:43][CH3:44])[CH:38]=1

参加物

7

反応物 5

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 114613-Methoxybenzoic AcidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate

生成物 1

HCID 66589702N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-3-methoxy-benzamide収率 59.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

1-Chloro-N,N,2-trimethylprop-1-en-1-amine (89 μl, 0.67 mmol, 1.05 eq) was added dropwise to 3-methoxybenzoic acid (97 mg, 0.63 mmol, 1 eq) in DCM (1.5 ml) at ambient temperature. After stirring at ambient temperature for 1.5 h, a solution of tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (199 mg, 0.57 mmol, 0.9 eq) and pyridine (142 μL, 1.74 mmol, 2.75 eq) in DCM (2 ml) was added to the reaction mixture and stirring was continued at ambient temperature for a further 3 h. A solution of TFA (386 μL, 5.2 mmol, 8.25 eq) in DCM (3.5 ml) was then added and stirring was continued at ambient temperature for 18 h. The reaction mixture was 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 colourless solid (129 mg, 59% yield). 1H NMR (399.902 MHz, DMSO) δ 2.89 (4H, s), 3.73 (6H, s), 3.84 (3H, s), 6.34-6.33 (1H, m), 6.43 (2H, d), 6.48 (1H, s), 7.12-7.10 (1H, m), 7.42-7.37 (1H, m), 7.59-7.56 (2H, m), 10.65 (1H, br.s), 12.16 (1H, br.s). MS: m/z 382 (MH+).

後処理

  1. stirringstirring
  2. waitwas continued at ambient temperature for a further 3 h
  3. stirringstirring
  4. waitwas continued at ambient temperature for 18 h
  5. concentrationThe reaction mixture was concentrated
  6. customthe crude product was purified by reverse-phase prep
  7. customevaporated

出典と根拠

ORDレコード
ord-a9c95132fb3e4cd19d400bfe0fab8245
出典データセット
uspto-grants-2010_06
特許番号
US07737149B2

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