Dimethylformamide → [2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(4-furan-3-ylmethyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1877411Notes

Reaction equation

HRID 1877411 reaction equation
COC(C1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([C:15]([C:17]2[C:18]([O:24][C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=3[Cl:32])=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)=[O:16])[CH2:7]C1)=O.[O:33]1[CH:37]=[CH:36][C:35]([CH:38]=O)=[CH:34]1.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1.[CH3:58][N:59](C=O)C>>[Cl:32][C:26]1[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=1[O:24][C:18]1[C:17]([C:15]([N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:59]([CH2:38][C:35]3[CH:36]=[CH:37][O:33][CH:34]=3)[CH2:58][CH2:7]2)=[O:16])=[CH:22][C:21]([F:23])=[CH:20][N:19]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 103513-FuraldehydeHCID 12688Dibutyltin dichlorideHCID 12752PhenylsilaneHCID 592944731-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid methyl ester

Product 1

HCID 59294529[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(4-furan-3-ylmethyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanoneYield 18%

Conditions

Temperature
150 °C

Procedure

To a solution of [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (25.1 mg, 0.06 mmol, 1.0 equiv; Example 148) in anhydrous DMF (1 mL) was added furan-3-carbaldehyde (23.1 mg, 20 μL, 0.24 mmol, 4.0 equiv; [CAS RN 498-60-2]), dibutyltin dichloride (1.8 mg, 0.006 mmol, 0.1 equiv; [CAS RN 683-18-1]) and phenylsilane (13.0 mg, 15 μL, 0.12 mmol, 2.0 equiv; [CAS RN 694-53-1]). The reaction mixture was heated by microwave irradiation to 150° C. for 15 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 5.4 mg (18%) of the title compound as a light yellow solid. MS (ISP): 498.3 [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-f14cb233ffb44f9f83776e2527f35cb4
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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