Triethylamine → HCID 11525138, 화합물

HRID 499176

반응식

HRID 499176 반응식
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:25]=[CH:24][CH:23]=[CH:22][C:4]=1[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[N:18]=[N:17][C:16]([C:19](O)=[O:20])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)=[O:6].S(Cl)(Cl)=O.O[NH:33][C:34](=[NH:38])[CH2:35][CH2:36][CH3:37].C(N(CC)CC)C>C(Cl)(Cl)Cl.CN(C=O)C.ClCCl>[CH2:35]([C:34]1[N:38]=[C:19]([C:16]2[N:17]=[N:18][C:13]([N:10]3[CH2:9][CH2:8][N:7]([C:5]([C:4]4[CH:22]=[CH:23][CH:24]=[CH:25][C:3]=4[C:2]([F:27])([F:26])[F:1])=[O:6])[CH2:12][CH2:11]3)=[CH:14][CH:15]=2)[O:20][N:33]=1)[CH2:36][CH3:37]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 45487370HCID 45487370, 화합물HCID 178449909HCID 178449909, 화합물

생성물 1

HCID 11525138HCID 11525138, 화합물수율 39%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6212Chloroform용매HCID 6344Dichloromethane용매2회

실험 절차

To a suspension of 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (0.500 g, 1.314 mmol) in chloroform, one drop of DMF was added followed by the addition of thionyl chloride (0.5 mL). The mixture was heated at reflux overnight. The clear solution was evaporated to dryness under vacuum to get a pale yellow syrup. This syrup was then dissolved in anhydrous dichloromethane (1 mL) and transferred to a solution containing N-hydroxybutyramidine (0.134 g, 1.314 mmol) and triethylamine (0.5 mL) in dichloromethane (5 mL) at 0° C. The mixture was warmed up to room temperature and stirred for another 30 minutes. The solvent was removed in vacuo. The crude mixture was suspended in 1,4-dioxane-water (1:1, 9 mL) containing cesium carbonate (0.3 g) and heated at reflux overnight, cooled, concentrated and diluted with water (10 mL), extracted with ethyl acetate. The organic phase was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography and recrystallization from ethyl acetate-hexanes. The title compound was obtained as a white solid in 39% yield (0.228 g). m.p. 226° C. 1H NMR (300 MHz, CDCl3) 7.98 (d, J=9.6 Hz, 1H), 7.71 (d, J=7.7 Hz, 1H), 7.65-7.50 (m, 2H), 7.34 (d, J=7.4 Hz, 1H), 6.97 (d, J=9.6 Hz, 1H), 4.11-3.98 (m, 1H), 3.96-3.70 (m, 5H), 3.34 (t, J=5.1 Hz, 2H), 2.77 (t, J=7.4 Hz, 2H), 1.90-1.75 (m, 2H), 0.99 (t, J=7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 172.6, 171.1, 167.7, 159.2, 139.7, 134.1, 132.4, 129.5, 127.8, 127.2, 126.9, 126.8, 111.3, 46.3, 44.5, 44.1, 41.2, 27.9, 20.4, 13.7. MS (ES+) m/z 447.0 (M+1).

후처리

  1. additionwas added
  2. temperatureThe mixture was heated
  3. temperatureat reflux overnight
  4. customThe clear solution was evaporated to dryness under vacuum
  5. customto get a pale yellow syrup
  6. customThe solvent was removed in vacuo
  7. additioncontaining cesium carbonate (0.3 g)
  8. temperatureheated
  9. temperatureat reflux overnight
  10. temperaturecooled
  11. concentrationconcentrated
  12. additiondiluted with water (10 mL)
  13. extractionextracted with ethyl acetate
  14. dry with materialThe organic phase was dried over anhydrous Na2SO4
  15. concentrationconcentrated
  16. customThe residue was purified by column chromatography and recrystallization from ethyl acetate-hexanes

출처 및 근거

ORD 기록
ord-bda24d2bb4224c8c81734ee2ab5d927b
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07767677B2

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