1,4-Dioxane → 9-Fluoro-1-methyl-7-(4-methylpyridin-3-yl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

HRID 1521632ノート

反応式

HRID 1521632 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2.[CH3:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1B(O)O.O1CCOCC1.C([O-])(=O)C.[K+]>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].O>[F:12][C:10]1[CH:11]=[C:2]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][C:18]=2[CH3:17])[CH:3]=[C:4]2[C:9]=1[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 517044Potassium AcetateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 709780527-Bromo-9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

生成物 1

HCID 665757439-Fluoro-1-methyl-7-(4-methylpyridin-3-yl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of 7-bromo-9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline (109-5; 1.8 g, 0.0063 mol) and (4-methylpyridin-3-yl)boronic acid (1.73 g, 0.0127 mol) in the mixture of 1,4-dioxan (10 mL) and water (10 mL) was added potassium acetate (1.88 g, 0.0191 mol). Reaction mass was purged with argon for 20 min. Then catalyst Pd(dppf)2Cl2 (0.260 g, 0.000319 mol) was added and allowed to stir at 100° C. for 12 h. The reaction mixture was filtered through CELITE bed and filter bed was thoroughly washed with ethyl acetate. The collected organic parts was concentrated under vacuum to afford the crude compound, which was purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO-d6) 8.46-8.44 (d, J=8 Hz, 1H), 8.422 (s, 1H), 7.52-7.48 (d, J=16 Hz, 1H), 7.423 (s, 1H), 7.36-7.35 (d, J=4 Hz, 1H), 2.99 (m, 4H), 2.52 (s, 3H), 2.31 (s, 3H). HPLC purity 98.68%, MS (M+1): 294.7.

後処理

  1. customReaction mass
  2. customwas purged with argon for 20 min
  3. filtrationThe reaction mixture was filtered through CELITE bed
  4. filtrationfilter bed
  5. washwas thoroughly washed with ethyl acetate
  6. concentrationThe collected organic parts was concentrated under vacuum
  7. customto afford the crude compound, which
  8. customwas purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-b506e83c5c084d68897ed07c34ccbee1
出典データセット
uspto-grants-2015_07
特許番号
US09073929B2

反応ノート

読み込み中…