Nicotinamidine hydrochloride → HCID 178506365、化合物

HRID 1475194ノート

反応式

HRID 1475194 の反応式
[CH2:1]([NH:8][NH:9][C:10]([C:12]1[O:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[N:13]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:29](=N)([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=1.[OH-:38].[Na+].[CH2:40]([OH:42])C>>[F:27][C:24]([F:25])([F:26])[C:40]([O-:42])=[O:38].[CH2:1]([N:8]1[C:29]([C:30]2[CH:31]=[NH+:32][CH:33]=[CH:34][CH:35]=2)=[N:36][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

4

反応物 3

HCID 202042Nicotinamidine hydrochlorideHCID 23692425Sodium hydroxide ethanolHCID 86711886N'-benzyl-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carbohydrazide

生成物 1

HCID 178506365HCID 178506365、化合物収率 5.7%

反応条件

温度
65 °C

実験手順

A mixture of N′-benzyl-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carbohydrazide (40 mg, 0.11 mmol) and nicotinimidamide hydrochloride (33 mg, 0.21 mmol) in 2N NaOH ethanol solution (1.1 mL, 0.21 mmol) was heated to 65° C. for 30 min. The mixture was cooled to RT and concentrated under reduced pressure. The crude mixture was taken up in NMP (0.5 mL) and heated to 140° C. for 2 h. The mixture was cooled to RT and partitioned between H2O (0.5 mL) and EtOAc (0.5 mL). The aqueous layer was extracted with EtOAc (3×0.5 mL). The combined organic layers were washed with H2O (3×0.5 mL) and brine (0.5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude oil was purified by reverse-phase HPLC to provide the TFA salt as a white solid (1.8 mg, 3%): 1H NMR (600 MHz, CDCl3) δ ppm 8.93 (s, 1H), 8.79 (d, J=4.8 Hz, 1H), 8.29 (d, J=8.1 Hz, 2H), 8.08 (d, J=8.0 Hz, 1H), 7.52 (app. dd, J=7.5 Hz, 5.5 Hz, 1H), 7.37-7.30 (m, 5H), 7.20 (d, J=7.3 Hz, 2H), 5.62 (s, 2H); MS (ES+) C23H15F3N6O2 requires: 464. found: 465 [M+H]+.

後処理

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated under reduced pressure
  3. temperatureheated to 140° C. for 2 h
  4. temperatureThe mixture was cooled to RT
  5. custompartitioned between H2O (0.5 mL) and EtOAc (0.5 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (3×0.5 mL)
  7. washThe combined organic layers were washed with H2O (3×0.5 mL) and brine (0.5 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude oil was purified by reverse-phase HPLC

出典と根拠

ORDレコード
ord-e2d15a5b2e134a5dabf6cd855d003036
出典データセット
uspto-grants-2015_04
特許番号
US09018380B2

反応ノート

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