Hydrochloric Acid → 1-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dione

HRID 2251986

반응식

HRID 2251986 반응식
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16](=[O:18])[CH3:17].CON(C)[C:22]([C:24]1[N:25]=[N:26][N:27]([CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:28]=1[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)=[O:23].Cl>C1COCC1>[F:45][C:42]([F:43])([F:44])[C:40]1[CH:41]=[C:36]([CH:37]=[C:38]([C:46]([F:47])([F:49])[F:48])[CH:39]=1)[CH2:35][N:27]1[C:28]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[C:24]([C:22](=[O:23])[CH2:17][C:16]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Cl:9])=[O:18])[N:25]=[N:26]1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 72864Ethanone, 1-(2-chlorophenyl)-HCID 2724682Lithium diisopropylamideHCID 86601237HCID 86601237, 화합물

생성물 1

HCID 866012491-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dione수율 69%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Add lithium diisopropylamide (6 mL, 1.0 M in THF) to a solution of 1-(2-chloro-phenyl)-ethanone (0.929 g, 6.01 mmol) in THF (10 mL) at −78° C. and stir for 30 min. To the above enolate solution at −78° C., add a solution of 1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid methoxy-N-methyl-amide (1.29 g, 2.81 mmol) in THF (15 mL) via cannula. Warm solution to 70° C. and stir for 4 hours, than add 1N HCl (6 mL) and stir for an additional 30 min. Concentrate the mixture in vacuo to ¼ volume, dilute with EtOAc (60 mL) and wash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL). Dry, filter, and concentrate the organic phase and purify the crude material by flash chromatography using a linear gradient of 20% to 80% EtOAc/hexanes to give the title compound (1.07 g, 69%) as an orange foam. MS (IS) 553.2 (M+1), MS (ES−) 551.2 (M−1). 1H NMR (400 MHz, CDCl3): δ 15.5 (m, 1H), 7.78 (dd, 1H, J=1.3, 4.8), 8.54 (d, 1H, J=2.2), 7.81 (s, 1H), 7.64 (dd, 1H, J=2.0, 7.7), 7.57 (dt, 1H, J=2.0, 7.9), 7.44 (m, 4H), 7.38 (dt, 1H, J=1.8, 7.5), 7.33 (dt, 1H, J=1.5, 7.5), 7.19 (s, 1H), 5.59 (s, 2H).

후처리

  1. stirringWarm solution to 70° C. and stir for 4 hours
  2. stirringstir for an additional 30 min
  3. concentrationConcentrate the mixture in vacuo
  4. additiondilute with EtOAc (60 mL)
  5. washwash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL)
  6. customDry
  7. filtrationfilter
  8. concentrationconcentrate the organic phase
  9. custompurify the crude material by flash chromatography

출처 및 근거

ORD 기록
ord-5d45546754bb42fcb64387fa4583a837
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07320994B2

연결된 노트

불러오는 중…