Dichloromethane → HCID 66576851, compound

HRID 1521626Notes

Reaction equation

HRID 1521626 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]2[C:11]=1[N:10]1[C:12]([CH3:15])=[N:13][N:14]=[C:9]1[CH2:8][CH2:7]2.Br[C:26]1[CH:27]=[N:28][CH:29]=[C:30]([F:34])[C:31]=1[CH2:32][CH3:33].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:26]2[CH:27]=[N:28][CH:29]=[C:30]([F:34])[C:31]=2[CH2:32][CH3:33])[CH:5]=[C:6]2[C:11]=1[N:10]1[C:12]([CH3:15])=[N:13][N:14]=[C:9]1[CH2:8][CH2:7]2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 707011733-Bromo-4-ethyl-5-fluoropyridineHCID 70977855HCID 70977855, compound

Product 1

HCID 66576851HCID 66576851, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 9-chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline (80-4; 0.717 g, 0.0020 mol) and 3-bromo-4-ethyl-5-fluoropyridine (0.423 g, 0.0020 mol) in the mixture of 1,4-dioxan (5 mL) and water (5 mL) was added sodium carbonate (0.66 g, 0.0062 mol). Reaction mass was purged with argon for the next 20 min. Catalyst Pd(dppf)2Cl2.dichloromethane (0.084 g, 0.0001 mol) was added and again purged with argon for 10 min and allowed to stirred at 90° C. for 4 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): MeOH, flow rate: 1.0 mL/min, gradient T/% B:0/20,6/25,25/75,27/20,30/20) to obtain title compound. 1H NMR (400 MHz, DMSO-d6) δ: 8.55 (s, 1H), 8.32 (s, 1H), 7.64 (s, 1H), 7.55 (s, 1H), 2.94 (bs, 4H), 2.65-2.59 (m, 2H), 2.56 (s, 3H), 1.09-1.05 (t, J=7.6 Hz, 3H). MS (M+1): 343.2.

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-43209d991f25481cb433cd014fd5407b
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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