Cesium carbonate → HCID 86683144, compound

HRID 920931Notes

Reaction equation

HRID 920931 reaction equation
Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH2:13][CH2:14][C:15]1[N:16]=[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]3[CH:23]=1)[N:8]=[CH:7]2.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:76][C@@H:77]1[CH2:81][CH2:80][N:79]([C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:78]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:16]1[C:15]([CH2:14][CH2:13][N:9]2[C:10](=[O:12])[C:11]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[NH:76][C@@H:77]3[CH2:81][CH2:80][N:79]([C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:78]3)[CH:7]=[N:8]2)=[CH:23][N:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 866831451(2H)-Phthalazinone, 8-chloro-2-(2-imidazo[1,2-a]pyridin-2-ylethyl)-

Product 1

HCID 86683144HCID 86683144, compoundYield 24.73%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A reaction tube was charged with 8-chloro-2-(2-(imidazo[1,2-a]pyridin-2-yl)ethyl)phthalazin-1(2H)-one (155 mg, 0.48 mmol), BINAP (17.83 mg, 0.029 mmol), tris(dibenzylideneacetone)dipalladium(0) (8.74 mg, 9.55 μmol) and cesium carbonate (311 mg, 0.955 mmol) in 1591 μl of toluene. The mixture was stirred for 1 h under argon. To this mixture, (R)-tert-butyl 3-aminopyrrolidine-1-carboxylate (89 mg, 0.477 mmol) was added. The reaction mixture was heated in a microwave at 105° C. for 20 h. After completion of the reaction, the reaction mixture was extracted with water and DCM. The organic layers were washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography using a normal phase Companion® system (4 g gold, gradient elution: DCM to 10% methanol). Yield: 24.73%. LC-MS: m/e=475.2 (M+H)+.

Workup

  1. customAfter completion of the reaction
  2. extractionthe reaction mixture was extracted with water and DCM
  3. washThe organic layers were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography
  8. washa normal phase Companion® system (4 g gold, gradient elution: DCM to 10% methanol)

Sources & evidence

ORD record
ord-5c22ba2f0a80432bb58ba0329ca41ebb
Source dataset
uspto-grants-2016_03
Patent number
US09273068B2

Reaction notes

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