Cesium carbonate → 2-(Pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one

HRID 655475노트

반응식

HRID 655475 반응식
Br[C:2]1[C:6](=[O:7])[C:5]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[O:4][C:3]=1[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1.CC1(C)C(C)(C)OB([C:26]2[CH:43]=[CH:42][C:29]([O:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)=[CH:28][CH:27]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:15]1[CH:16]=[CH:17][C:12]([C:3]2[O:4][C:5]3([CH2:11][CH2:10][CH2:9][CH2:8]3)[C:6](=[O:7])[C:2]=2[C:26]2[CH:27]=[CH:28][C:29]([O:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)=[CH:42][CH:43]=2)=[CH:13][CH:14]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548103-Bromo-2-(pyridin-4-yl)-1-oxaspiro[4.4]non-2-en-4-one

생성물 1

HCID 593547962-(Pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one수율 6.6%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

A mixture of 3-bromo-2-(pyridin-4-yl)-1-oxaspiro[4.4]non-2-en-4-one (0.2 g, 0.68 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.25 g, 0.82 mmol), and Cs2CO3 (1.25 g, 6.68 mmol) in toluene (10 mL) and water (2 mL) was degassed, Pd(dppf)Cl2 (0.05 g, 0.014 mmol) was added under an inert atmosphere and again degassed. Then the reaction was refluxed for 3 h. and was filtered through a pad of Celite®, the filtrate was diluted with EtOAc (50 mL), washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 2-(pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one (20 mg, 5%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.68 (d, J=8.5 Hz, 2H), 8.44 (d, J=7.9 Hz, 1H), 8.02 (t, J=8.4 Hz, 2H), 7.80 (t, J=8.2 Hz, 1H), 7.68 (d, J=8.2 Hz, 1H), 7.63 (t, J=8.5 Hz, 1H), 7.48 (d, J=8.5 Hz, 2H), 7.18 (d, J=7.4 Hz, 2H), 7.12 (d, J=7.5 Hz, 2H), 5.42 (s, 2H), 2.08-1.82 (m, 8H). MS: [M+H]: m/z=449.2. HPLC: 96.9% (RT-2.24 min), Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).

후처리

  1. customwas degassed
  2. customagain degassed
  3. temperatureThen the reaction was refluxed for 3 h.
  4. filtrationwas filtered through a pad of Celite®
  5. additionthe filtrate was diluted with EtOAc (50 mL)
  6. washwashed with water (20 mL), brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto obtain the crude product
  11. customThe crude material was purified via silica gel column chromatography

출처 및 근거

ORD 기록
ord-0e718d0b8da4495386d6581d01fac42e
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071595B2

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