Sodium hydride → 3-Iodo-1'-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 588728Notes

Reaction equation

HRID 588728 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:5]=[C:6]2[CH2:21][C@@:11]3([C:19]4[C:14](=[N:15][CH:16]=[CH:17][CH:18]=4)[NH:13][C:12]3=[O:20])[CH2:10][C:7]2=[N:8][CH:9]=1.[CH3:22][Si:23]([CH3:30])([CH3:29])[CH2:24][CH2:25][O:26][CH2:27]Cl>CN(C=O)C>[I:3][C:4]1[CH:5]=[C:6]2[CH2:21][C:11]3([C:19]4[C:14](=[N:15][CH:16]=[CH:17][CH:18]=4)[N:13]([CH2:27][O:26][CH2:25][CH2:24][Si:23]([CH3:30])([CH3:29])[CH3:22])[C:12]3=[O:20])[CH2:10][C:7]2=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58118681(6S)-3-Iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2' (1'H)-one2×

Product 1

HCID 1317344363-Iodo-1'-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (0.242 g, 6.06 mmol) was added portionwise to a solution of (6S)-3-iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (described in Intermediate 4) (2.00 g, 5.51 mmol) in DMF (50 mL) at 0° C. After stirring for 10 min, 2-(trimethylsilyl)ethoxymethyl chloride (1.01 g, 6.06 mmol) was added dropwise. The resulting mixture was warmed slowly to ambient temperature and stirred for 48 h. The reaction was partitioned between water (20 mL) and EtOAc (100 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (30 mL). The combined organic extracts were washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—95:5 to 50:50, to give the title compound. MS: m/z=493.9 (M+1).

Workup

  1. stirringstirred for 48 h
  2. customThe reaction was partitioned between water (20 mL) and EtOAc (100 mL)
  3. customThe organic layer was removed
  4. extractionthe aqueous phase was extracted further with EtOAc (30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with a gradient of hexanes

Sources & evidence

ORD record
ord-692d8b7b1e9940708ad137333234d81a
Source dataset
uspto-grants-2016_01
Patent number
US09227972B2

Reaction notes

Loading…