Sodium Carbonate → 6-Cyclopropyl-7-(5-fluoropyridin-3-yl)-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

HRID 1521668Notes

Reaction equation

HRID 1521668 reaction equation
Br[C:2]1[C:3]([CH:16]2[CH2:18][CH2:17]2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[C:12]([CH3:15])=[N:13][N:14]=[C:7]1[CH2:6][CH2:5]2.[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[N:24][CH:25]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>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>[CH:16]1([C:3]2[C:2]([C:22]3[CH:23]=[N:24][CH:25]=[C:20]([F:19])[CH:21]=3)=[CH:11][CH:10]=[C:9]3[C:4]=2[CH2:5][CH2:6][C:7]2[N:8]3[C:12]([CH3:15])=[N:13][N:14]=2)[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 709779917-Bromo-6-cyclopropyl-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

Product 1

HCID 899617136-Cyclopropyl-7-(5-fluoropyridin-3-yl)-1-methyl-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
80 °C

Procedure

To a stirred solution of 7-bromo-6-cyclopropyl-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline (147-8; 0.250 g, 0.00082 mol) and (5-fluoropyridin-3-yl)boronic acid (0.126 g, 0.009 mol) in the mixture of 1,4-dioxane (10 mL) and water (10 mL) was added sodium carbonate (0.260 g, 0.00246 mol). Reaction mass was purged with argon for 20 min. Then catalyst Pd(dppf)2Cl2 (0.066 g, 0.000082 mol) was added and allowed to stir at 80° C. for 12 h. The reaction mixture was filtered through CELITE bed and filter bed was thoroughly washed with ethyl acetate. The collected organic layer 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) δ 8.587-8.580 (d, J=2.8 Hz, 1H), 8.548 (s, 1H), 7.881-7.856 (d, J=10 Hz, 1H), 7.679-7.658 (d, J=8.4 Hz, 1H), 7.401-7.380 (d, J 8.4 Hz, 1H), 3.237-3.203 (t, J=6.8 Hz, 2H), 3.050-3.016 (t, J=7.2 Hz, 2H), 2.671 (s, 3H), 2.175 (s, 1H), 0.759-0739 (d, J 8 Hz, 2H), 0.034-0.022 (d, J=4.8 Hz, 2H), MS (M+1): 321.2.

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 layer was concentrated under vacuum
  7. customto afford the crude compound, which
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2634feb02a74447f9c4bc63faa675067
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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