Dichloromethane → 7-(4-Ethyl-5-fluoropyridin-3-yl)-6-fluoro-1-methyl-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinoline

HRID 1521661Notes

Reaction equation

HRID 1521661 reaction equation
Br[C:2]1[C:3]([F:16])=[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.[CH2:17]([C:19]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][N:22]=[CH:21][C:20]=1[F:34])[CH3:18].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O.O1CCOCC1>[CH2:17]([C:19]1[C:20]([F:34])=[CH:21][N:22]=[CH:23][C:24]=1[C:2]1[C:3]([F:16])=[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)[CH3:18]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 709774807-Bromo-6-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolineHCID 709778534-Ethyl-3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 899618507-(4-Ethyl-5-fluoropyridin-3-yl)-6-fluoro-1-methyl-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 7-bromo-6-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline (146-7; 0.2 g, 0.00704 mol) and 4-ethyl-3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.21 g, 0.0084 mol) in the mixture of 1,4-dioxan (5 mL) and water (5 mL) was added sodium carbonate (0.186 g, 0.0176 mol). Reaction mass was purged with argon for the next 20 min. Catalyst Pd(dppf)2Cl2.dichloromethane (0.28 g, 0.00352 mol) was added and again purged with argon for 10 min 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 followed by preparative HPLC (analytical conditions: column: ZORBAX XDB (150 mm×4.6 mm×3.5 μm), mobile phase (A): water, mobile phase (B): methanol, flow rate: 1.0 mL/min, gradient T/% B:0/20,8/70,25/70,27/20,30/20) to obtain title compound. 1H NMR (400 MHz, CDCl3-d6) δ 8.451 (s, 1H), 8.238 (s, 1H), 7.427-7.406 (d, J=8.4 Hz, 1H), 7.297-7.278 (d, J=7.6 Hz, 1H), 3.219-3.184 (t, J=6.4 Hz, 2H), 3.132-3.097 (t, J=7.6 Hz, 2H), 2.812 (s, 3H), 2.604-2.586 (d, J=7.2 Hz, 2H), 1.130-1.093 (t, J=7.6 Hz, 3H). MS (M+1): 327.1.

Workup

  1. customReaction mass
  2. customwas purged with argon for the next 20 min
  3. customagain purged with argon for 10 min
  4. filtrationThe reaction mixture was filtered through CELITE bed
  5. filtrationfilter bed
  6. washwas thoroughly washed with ethyl acetate
  7. concentrationThe collected organic parts was concentrated under vacuum
  8. customto afford the crude compound, which
  9. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0a847912ac064e948d6899e21159d350
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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