Sodium hydride → 3-(2-Chloro-6-fluorophenyl)-1-(4-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-one

HRID 59455노트

반응식

HRID 59455 반응식
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[N:8][OH:9])[NH2:7])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:22]1[NH:26][C:25](=[O:27])[N:24]([C:28]2[CH:37]=[CH:36][C:31]([C:32](OC)=O)=[C:30]([O:38][CH3:39])[CH:29]=2)[N:23]=1>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:22]1[NH:26][C:25](=[O:27])[N:24]([C:28]2[CH:37]=[CH:36][C:31]([C:32]3[O:9][N:8]=[C:6]([C:5]4[CH:10]=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:7]=3)=[C:30]([O:38][CH3:39])[CH:29]=2)[N:23]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 2246504-chloro-N'-hydroxybenzenecarboximidamideHCID 136492448methyl 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate

생성물 1

HCID 1366125233-(2-Chloro-6-fluorophenyl)-1-(4-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-one수율 11.6%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a solution of 4-chloro-N′-hydroxybenzimidamide (Intermediate-19, 0.069 g, 0.39 mmol) in dry toluene was added sodium hydride (0.016 g, 0.39 mmol). The reaction mixture was refluxed for 30 minutes followed by addition of methyl 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (step-2 of Intermediate-15, 0.100 g, 0.26 mmol). The reaction mixture was refluxed for 5-6 h. The reaction mixture was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford crude product which was further purified by column chromatography to afford 0.015 g of desired product. 1H NMR (DMSO-d6): δ 3.98 (s, 3H), 7.45-7.48 (m, 1H), 7.54 (d, J=8.1 Hz, 1H), 7.67 (d, J=8.4 Hz, 3H), 7.83 (d, J=8.1 Hz, 1H), 7.95 (s, 1H), 8.10 (d, J=8.4 Hz, 2H), 8.18 (d, J=8.7 Hz, 1H), 12.90 (br s, 1H). MS [M+H]+: 499.89.

후처리

  1. temperatureThe reaction mixture was refluxed for 30 minutes
  2. temperatureThe reaction mixture was refluxed for 5-6 h
  3. customThe reaction mixture was quenched in water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customto afford crude product which
  8. customwas further purified by column chromatography

출처 및 근거

ORD 기록
ord-019c3838a7324a1ab4c029ed11690aa4
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09439890B2

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