Toluene → {4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acid ethyl ester

HRID 1877412Notes

Reaction equation

HRID 1877412 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH2:15][CH2:14]2)=[O:12])=[CH:9][C:8]([F:23])=[CH:7][N:6]=1.[CH2:29]([O:31][C:32](=[O:35])[CH:33]=O)[CH3:30].C1(C)C=CC=CC=1.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1>>[CH2:29]([O:31][C:32](=[O:35])[CH2:33][N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:13]([C:11]([C:10]2[C:5]([O:4][C:3]3[CH:24]=[C:25]([Cl:28])[CH:26]=[CH:27][C:2]=3[Cl:1])=[N:6][CH:7]=[C:8]([F:23])[CH:9]=2)=[O:12])[CH2:14][CH2:15]1)[CH3:30]

Participants

6

Reactant 5

HCID 1140TolueneHCID 12688Dibutyltin dichlorideHCID 12752PhenylsilaneHCID 70211Ethyl oxoacetateHCID 59294514[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 59294509{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acid ethyl esterYield 34%

Conditions

Temperature
100 °C

Procedure

To [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (200 mg, 0.478 mmol, 1.0 equiv; Example 147) was added a 50% solution of glyoxylic acid ethylester in toluene (1.03 g, 1 mL, 1.913 mmol, 4.0 equiv; [CAS RN 924-44-7]), dibutyltin dichloride (14.6 mg, 0.048 mmol, 0.1 equiv; [CAS RN 683-18-1]) and phenylsilane (103.8 mg, 118 μL, 0.956 mmol, 2.0 equiv; [CAS RN 694-53-1]). The reaction mixture was heated by microwave irradiation to 100° C. for 30 min. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 82.7 mg (34%) of the title compound as a light yellow solid. MS (ISP): 504.3 [M+H]+.

Workup

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-85eeee2f283d4f1686adbd2f36a12035
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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