Sodium hydride → 10-methyl-7-(2-(6-methylpyridin-3-yl)ethyl)-2,3,5,6,7,11c-hexahydro-1H-pyrido[3',2':4,5]pyrrolo[2,3-g]indolizine

HRID 1469449Notes

Reaction equation

HRID 1469449 reaction equation
[CH3:1][C:2]1[CH:17]=[N:16][C:5]2[NH:6][C:7]3[CH2:8][CH2:9][N:10]4[CH:14]([C:15]=3[C:4]=2[CH:3]=1)[CH2:13][CH2:12][CH2:11]4.[H-].[Na+].CC1C=CC(S(O[CH2:31][CH2:32][C:33]2[CH:34]=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=2)(=O)=O)=CC=1>CN(C=O)C.O>[CH3:1][C:2]1[CH:17]=[N:16][C:5]2[N:6]([CH2:31][CH2:32][C:33]3[CH:34]=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=3)[C:7]3[CH2:8][CH2:9][N:10]4[CH:14]([C:15]=3[C:4]=2[CH:3]=1)[CH2:13][CH2:12][CH2:11]4

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 674346819-methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluoreneHCID 866581512-(6-Methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 5845988610-methyl-7-(2-(6-methylpyridin-3-yl)ethyl)-2,3,5,6,7,11c-hexahydro-1H-pyrido[3',2':4,5]pyrrolo[2,3-g]indolizine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 10-methyl-2,3,5,6,7,11c-hexahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizine (110 mg, 0.484 mmol) in DMF (1 mL) was added a suspension of NaH (60.0 mg, 1.45 mmol) in DMF (1 mL). After stirring for 5 min at RT, a solution of 2-(6-methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate (423 mg, 1.45 mmol) in DMF (1 mL) was added dropwise into the reaction mixture and stirring continued for another 2 h. The progress of reaction was monitored by TLC and LCMS. 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 reverse phase HPLC to yield 10-methyl-7-(2-(6-methylpyridin-3-yl)ethyl)-2,3,5,6,7,11c-hexahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizine. 1H NMR (CD3OD, Tri-HCl salt) δ (ppm): 8.7 (s, 1H), 8.4 (d, 1H), 8.25 (s, 2H), 7.8 (d, 1H), 5.1 (m, 1H), 4.8-4.6 (m, 2H), 3.9-3.7 (m, 3H), 3.4 (m, 2H), 3.4-3.2 (m, 2H), 2.9-2.7 (m, 2H), 2.8 (s, 3H), 2.5 (s, 3H), 2.3-2.15 (m, 3H). Separation by chiral HPLC provided enantiomers 74a and 74b.

Workup

  1. stirringstirring
  2. waitcontinued for another 2 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 reverse phase HPLC

Sources & evidence

ORD record
ord-1afe91a21e2c486ca37d77fb763f5969
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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