Isobutyraldehyde → [2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-isobutyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1877399Notes

Reaction equation

HRID 1877399 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][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][CH:8]=[CH:7][N:6]=1.[CH3:28][CH:29]([CH3:32])[CH:30]=O.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1>CN(C=O)C>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][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)[N:16]([CH2:28][CH:29]([CH3:32])[CH3:30])[CH2:15][CH2:14]2)=[O:12])=[CH:9][CH:8]=[CH:7][N:6]=1

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 12688Dibutyltin dichlorideHCID 12752PhenylsilaneHCID 59294486[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 46195129[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-isobutyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanoneYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of [2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (24 mg, 0.06 mmol, 1.0 equiv; Example 122) in anhydrous DMF (1 mL) was added 2-methyl-propionaldehyde (17.3 mg, 22 μL, 0.24 mmol, 4.0 equiv; [CAS RN 78-84-2]), 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 10.3 mg (38%) of the title compound as a light yellow powder. MS (ISP): 456.4 [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-5e63784e56e74e6aa1f14c38f39b9fb0
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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