Triethylamine → N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamide

HRID 658575ノート

反応式

HRID 658575 の反応式
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.[OH:16][C:17]1[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH2:25][C:26](O)=[O:27])=[CH:19][C:18]=1[O:29][CH3:30].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.Cl>[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH:14][C:26](=[O:27])[CH2:25][C:20]3[CH:21]=[C:22]([O:23][CH3:24])[C:17]([OH:16])=[C:18]([O:29][CH3:30])[CH:19]=3)[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 780934-Hydroxy-3,5-dimethoxyphenylacetic acidHCID 2724699PyBOPHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

生成物 1

HCID 57422265N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamide収率 29%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒

実験手順

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (376 mg, 1.7 mmol), 2-(4-hydroxy-3,5-dimethoxyphenyl)acetic acid (350 mg, 1.7 mmol), PyBop (1 g, 2 mmol) and triethylamine (605 mg, 6 mmol) were stirred together in DMF (10 mL) at room temperature for 2 hours. The reaction mixture was diluted with aqueous 1N HCl (100 mL) and extracted with DCM (3×, 75 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated on the rotovap. The residue was purified by silica gel chromatography (30% ethyl acetate in hexanes) to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamide (189 mg, 29%) as a white solid. 1H NMR (CDCl3, 400 MHz) 2.10 (s, 3H), 2.36 (s, 3H), 3.40 (s, 2H), 3.70 (s, 6H), 5.07 (s, 2H), 6.53 (s, 2H), 7.39 (s, 1H), 7.92 (s, 1H), 8.18 (s, 1H), 10.03 (s, 1H). LC/MS; [M+H] calculated for C19H22N4O5; expected 387.16; found 387.6. Melting point: 187-188° C.

後処理

  1. extractionextracted with DCM (3×, 75 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated on the rotovap
  5. customThe residue was purified by silica gel chromatography (30% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-e3b0204e836f4e0db230762a44dc2991
出典データセット
uspto-grants-2011_12
特許番号
US08076491B2

反応ノート

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