Sodium hydride → 6-methyl-9-(2-(6-methylpyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c']dipyridine

HRID 1469558Notes

Reaction equation

HRID 1469558 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2[NH:8][C:9]3[C:14]([C:4]=2[CH2:3]1)=[CH:13][CH:12]=[CH:11][N:10]=3.[H-].[Na+].CC1C=CC(S(O[CH2:28][CH2:29][C:30]2[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=2)(=O)=O)=CC=1>CN(C=O)C.O>[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2[N:8]([CH2:28][CH2:29][C:30]3[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)[C:9]3[C:14]([C:4]=2[CH2:3]1)=[CH:13][CH:12]=[CH:11][N:10]=3

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 682836406-methyl-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c']dipyridineHCID 866581512-(6-Methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 682830806-methyl-9-(2-(6-methylpyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c']dipyridineYield 27.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 6-methyl-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c′]dipyridine (200 mg, 1.068 mmol) in DMF (1 mL) was added a suspension of NaH (128.0 mg, 3.24 mmol) in DMF (1 mL). After stirring for 5 min. at RT, a solution of 2-(6-methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate (932 mg, 3.204 mmol) in DMF (1 mL) was added dropwise into the reaction mixture and stirring continued for another 3 h. The progress of reaction was monitored by TLC and NMR. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (3×25 mL). The organic layer was washed with water (3×20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by silica gel flash chromatography eluting with 10% MeOH-DCM to yield 6-methyl-9-(2-(6-methylpyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c′]dipyridine (90 mg) as a free base. The free base was converted into tri-HCl salt by treatment with ethanolic HCl. 1H NMR (CD3OD, Tri-HCl salt) δ (ppm): 8.76 (s, 1H), 8.40 (m, 3H), 7.80 (d, 1H), 7.50 (t, 1H), 4.90-4.70 (m, 3H), 4.42 (m, 1H), 3.95 (m, 1H), 3.66 (m, 1H), 3.42-3.30 (m, 4H), 3.15 (s, 3H), 2.76 (s, 3H).

Workup

  1. stirringstirring
  2. waitcontinued for another 3 h
  3. customThe progress of reaction
  4. extractionextracted with EtOAc (3×25 mL)
  5. washThe organic layer was washed with water (3×20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude material, which
  9. customwas purified by silica gel flash chromatography
  10. washeluting with 10% MeOH-DCM

Sources & evidence

ORD record
ord-821c6d39098c478f886f6a9ce7648392
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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