Sodium Carbonate → Ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}thio)phenyl]-2-quinolinecarboxylate

HRID 2423537Notes

Reaction equation

HRID 2423537 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:13]([CH2:14][S:15][C:16]2[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=2)=[C:12]([CH:25]([CH3:27])[CH3:26])[O:11][N:10]=1.Br[C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[C:34]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:33]=[CH:32]2.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:13]([CH2:14][S:15][C:16]2[CH:21]=[CH:20][C:19]([C:29]3[CH:30]=[C:31]4[C:36](=[CH:37][CH:38]=3)[N:35]=[C:34]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:33]=[CH:32]4)=[CH:18][CH:17]=2)=[C:12]([CH:25]([CH3:27])[CH3:26])[O:11][N:10]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 53404703Ethyl 6-bromoquinoline-2-carboxylateHCID 59321491[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}thio)phenyl]boronic acid

Product 1

HCID 59321591Ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}thio)phenyl]-2-quinolinecarboxylateYield 23.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of crude [4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}thio)phenyl]boronic acid (76 mg, 0.18 mmol), ethyl 6-bromo-2-quinolinecarboxylate (42 mg, 0.15 mmol), tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.0006 mmol) in 1,2-dimethoxyethane (0.8 mL), and 2 M sodium carbonate (0.65 mL) was heated in a 70° C. oil bath for 1.5 hours. The solution was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried with magnesium sulfate filtered and concentrated. The residue was purified by silica gel chromatography (hexane to 2:5 ethyl acetate:hexanes gradient elution) to give 20 mg (22% as 0.4 ethyl acetate) of ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}thio)phenyl]-2-quinolinecarboxylate. 1H NMR (400 MHz, CDCl3): δ 8.38-8.32 (m, 2H), 8.21 (d, J=9 Hz, 1H), 7.98 (s, 1H), 7.96 (d, J=2 Hz, 1H), 7.59 (d, J=8 Hz, 2H), 7.43-7.32 (m, 5H), 4.57 (q, J=7 Hz, 2H), 3.82 (s, 2H), 3.07 (septet, J=7 Hz, 1H), 1.50 (t, J=7 Hz, 3H), 1.27 (d, J=7 Hz, 6H).

Workup

  1. customThe solution was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (hexane to 2:5 ethyl acetate:hexanes gradient elution)

Sources & evidence

ORD record
ord-a17f2a848169466490f810e116d830a1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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