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

HRID 1877414Notes

Reaction equation

HRID 1877414 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.[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:35]([O:37][C:38](=[O:42])[CH2:39][CH2:40]Br)[CH3:36]>CN(C=O)C>[CH2:35]([O:37][C:38](=[O:42])[CH2:39][CH2:40][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)[CH3:36]

Participants

5

Reactant 3

HCID 68320Ethyl 3-bromopropionateHCID 21226445Aluminium lithium hydrideHCID 59294514[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 592944813-{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-propionic acid ethyl esterYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 147) in anhydrous DMF (1 mL) was added lithium aluminium hydride (2.3 mg, 0.06 mmol, 1.0 equiv; [CAS RN 16853-85-3]) and the reaction mixture stirred at rt. After 30 min, 3-bromo-propionic acid ethyl ester (13.0 mg, 10 μL, 0.072 mmol, 1.2 equiv; [CAS RN 539-74-2]) was added and the reaction mixture heated by microwave irradiation to 150° 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 2.4 mg (8%) of the title compound as a light brown oil. MS (ISP): 518.3 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated by microwave irradiation to 150° C. for 30 min
  2. customRemoval of the solvent mixture
  3. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  4. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  5. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-0b5c8d4b7d5749259c6d283c0a831aad
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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