Cesium carbonate → (S)-isopropyl 4-(cyclopropanecarbonyl)-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate

HRID 1485703Notes

Reaction equation

HRID 1485703 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([N:6]([C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[C@@H:7]([CH3:18])[CH2:8][N:9]2[C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:3]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:44]2[CH:45]=[N:46][N:47](C(OC(C)(C)C)=O)[CH:48]=2)O1>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH:21]1([C:19]([N:6]2[C:5]3[C:10](=[CH:11][C:2]([C:44]4[CH:45]=[N:46][NH:47][CH:48]=4)=[CH:3][CH:4]=3)[N:9]([C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[CH2:8][C@@H:7]2[CH3:18])=[O:20])[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118078841(S)-isopropyl 7-bromo-4-(cyclopropanecarbonyl)-3-methyl-3,4-dihydroquinoxalin-1(2H)carboxylate

Product 1

HCID 118079118(S)-isopropyl 4-(cyclopropanecarbonyl)-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylateYield 71.1%

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A 50-mL round bottomed flask fitted with a nitrogen inlet and magnetic stir bar was charged with (S)-isopropyl 7-bromo-4-(cyclopropanecarbonyl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.801 g, 2.1 mmol), dioxane (11 mL), and water (4.6 mL). Cesium carbonate (2.053 g, 6.30 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-carboxylate (0.927 g, 3.15 mmol) were then added. The reaction was purged with nitrogen and bis(triphenylphosphine)palladium (II) dichloride (0.177 g, 0.252 mmol) was added. The mixture was heated at 90° C. with vigorous stirring for 5 h and then cooled to ambient temperature. Water (25 mL) was added, and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic extracts were concentrated to afford a viscous oil and purified via column chromatography (gradient elution with 75-100% ethyl acetate-hexanes). The resulting material was triturated with diethyl ether (2×10 mL) to afford (S)-isopropyl 4-(cyclopropanecarbonyl)-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.55 g, 71% yield) as a solid. MS (ESI, pos. ion) m/z 369 [M+1]+.

Workup

  1. customA 50-mL round bottomed flask fitted with a nitrogen inlet and magnetic stir bar
  2. additionwas added
  3. temperaturecooled to ambient temperature
  4. extractionthe mixture was extracted with ethyl acetate (3×25 mL)
  5. concentrationThe combined organic extracts were concentrated
  6. customto afford a viscous oil
  7. custompurified via column chromatography (gradient elution with 75-100% ethyl acetate-hexanes)
  8. customThe resulting material was triturated with diethyl ether (2×10 mL)

Sources & evidence

ORD record
ord-2c738d566753487398f08f195aa31a1f
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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