Water → (+/-)-Methyl 3-(2'-oxo-1',2',6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2-yl)benzoate

HRID 2262849Notes

Reaction equation

HRID 2262849 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]3[CH2:23][C:13]4([C:21]5[C:16](=[N:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12][C:7]=3[CH:8]=2)[N:3]=1.[CH3:24][O:25][C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)=[O:27].C(=O)([O-])[O-].[K+].[K+].O>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:22]=[C:14]1[NH:15][C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:21]2[C:13]21[CH2:12][C:7]1[CH:8]=[C:9]3[C:4](=[CH:5][C:6]=1[CH2:23]2)[N:3]=[C:2]([C:32]1[CH:33]=[C:28]([CH:29]=[CH:30][CH:31]=1)[C:26]([O:25][CH3:24])=[O:27])[CH:11]=[CH:10]3

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 59594283(+/-)-2-Chloro-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 1

HCID 16736990(+/-)-Methyl 3-(2'-oxo-1',2',6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2-yl)benzoate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A stirred mixture of (±)-2-chloro-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (204 mg, 0.634 mmol, described in Intermediate 20), 3-methoxycarbonylphenylboronic acid (229 mg, 1.27 mmol), PdCl2(PPh3)2 (44 mg, 0.063 mmol), and potassium carbonate (290 mg, 2.10 mmol), in 1,2-dimethoxyethane (3 mL) and H2O (1 mL) was heated at 80° C. for 18 h. The cooled mixture was partitioned between H2O (40 mL) and EtOAc (40 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (40 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The product-containing fractions were combined and concentrated to give the title compound. MS: m/z=422 (M+1). HRMS: m/z=422.1504; calculated m/z=422.1499 for C26H20N3O3.

Workup

  1. customThe cooled mixture was partitioned between H2O (40 mL) and EtOAc (40 mL)
  2. customThe organic layer was removed
  3. extractionthe aqueous phase was extracted further with EtOAc (40 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by HPLC
  9. washeluting with a gradient of H2O
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f17b779f16a24cdba55d6fe534454621
Source dataset
uspto-grants-2010_12
Patent number
US07851464B2

Reaction notes

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