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

HRID 2094856

반응식

HRID 2094856 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6228Dimethylformamide용매

실험 절차

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 C, 19; H, 22; N, 4; O, 5; expected 387.16; found 387.6. Melting point: 187-188° C.

후처리

  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)

출처 및 근거

ORD 기록
ord-82ca43c36b754652ada5680dd8433bc5
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445692B2

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