Diisopropylethylamine → [2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]quinoxalin-5-yl)-methanone

HRID 1877398Notes

Reaction equation

HRID 1877398 reaction equation
[CH:1]1[N:5]2[C:6]3[C:11]([NH:12][CH2:13][C:4]2=[CH:3][CH:2]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3.C(N(C(C)C)C(C)C)C.[Cl:23][C:24]1[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][C:25]=1[O:26][C:27]1[C:32]([C:33](N2C3C(=CC=CC=3)NCC2)=[O:34])=[CH:31][CH:30]=[CH:29][N:28]=1>C(O)C.[Pd]>[Cl:23][C:24]1[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][C:25]=1[O:26][C:27]1[C:32]([C:33]([N:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]3[CH2:1][CH2:2][CH2:3][CH:4]3[CH2:13]2)=[O:34])=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 118051814,5-Dihydropyrrolo[1,2-a]quinoxalineHCID 59294486[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 59294531[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]quinoxalin-5-yl)-methanoneYield 32.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of 4,5-dihydro-pyrrolo[1,2-α]quinoxaline (30.6 mg, 0.18 mmol, 1.2 equiv; [CAS RN 56721-86-9]) in ethanol (5 mL) was added palladium on carbon (3.2 mg, 0.003 mmol, 0.02 equiv; 10% Pd/C; [CAS RN 7440-05-3]) and the reaction mixture stirred under an atmosphere of hydrogen (3 bar) at rt for 4 h. The reaction mixture was concentrated under reduced pressure, filtered over Celite® and the remaining residue redissolved in anhydrous DMF (1 mL). To this solution was added N-ethyldiisopropylamine (64 mg, 86 μL, 0.50 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and 2-(2,5-dichloro-phenoxy)-nicotinoylchloride (45.4 mg, 0.15 mmol, 1.0 equiv; prepared according to Example 122) and the reaction mixture stirred at rt over night. 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 21.4 mg (32%) of the title compound. MS (ISP): 440.1 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. filtrationfiltered over Celite®
  3. dissolutionthe remaining residue redissolved in anhydrous DMF (1 mL)
  4. stirringthe reaction mixture stirred at rt over night
  5. customRemoval of the solvent mixture
  6. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  7. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  8. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-9219f11e0d454314afdad1913c4bf57b
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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