Cesium carbonate → (+/-)-2'-Oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-2-carbonitrile

HRID 1921168Notes

Reaction equation

HRID 1921168 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:11]#[N:12])=[N:7][C:8]=1[CH2:9]Br.[CH3:13][Si:14]([CH3:30])([CH3:29])[CH2:15][CH2:16][O:17][CH2:18][N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][C:20]1=[O:28].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[O:28]=[C:20]1[N:19]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:30])([CH3:29])[CH3:13])[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[C:21]21[CH2:9][C:8]1=[N:7][C:6]([C:11]#[N:12])=[CH:5][CH:4]=[C:3]1[CH2:2]2

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 574588861-{[2-(Trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one2×HCID 66812876HCID 66812876, compound

Product 1

HCID 57974064(+/-)-2'-Oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5,6-bis(bromomethyl)pyridine-2-carbonitrile from Step C (1.80 g, 6.21 mmol) and 1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (1.64 g, 6.21 mmol, described in Intermediate 1) in DMF (207 mL) was added cesium carbonate (6.07 g, 18.6 mmol), portionwise, over 5 min. After 18 h, the mixture was partitioned between CH2Cl2 (100 mL), saturated aqueous NaHCO3 (100 mL) and brine (200 mL). The organic layer was removed and the aqueous layer was extracted further with CH2Cl2 (2×100 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 10:90, to give the title compound. MS: m/z=393 (M+1).

Workup

  1. waitAfter 18 h
  2. customthe mixture was partitioned between CH2Cl2 (100 mL), saturated aqueous NaHCO3 (100 mL) and brine (200 mL)
  3. customThe organic layer was removed
  4. extractionthe aqueous layer was extracted further with CH2Cl2 (2×100 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-6d45bd695c084cbd9433b38c9f409736
Source dataset
uspto-grants-2012_05
Patent number
US08173655B2

Reaction notes

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