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

HRID 1521632Notes

Reaction equation

HRID 1521632 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b506e83c5c084d68897ed07c34ccbee1
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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