Sodium hydride → HCID 68284109, compound

HRID 1630587Notes

Reaction equation

HRID 1630587 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:5]=3[C:4]=2[CH:3]=1.[H-].[Na+].[O:19]1[CH2:21][CH:20]1[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:21][CH:20]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[OH:19])[C:6]3[CH2:11][CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 68252922HCID 68252922, compound

Product 1

HCID 68284109HCID 68284109, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 9-chloro-2-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (1 g, 4.273 mmol) in DMF was added NaH (512 mg, 12.81 mmol) in portions at 0° C. After stirring the reaction mixture at 0° C. for 15 min, a solution of 4-(oxiran-2-yl)pyridine (775 mg, 6.409 mmol) in DMF (1 mL) was added dropwise into the mixture at the same temperature and stirring continued at RT overnight. The progress of reaction was monitored by TLC and LCMS. After completion, ice water was added into the reaction mixture and extracted with EtOAc (3×50 mL). The organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography using 10% MeOH/DCM as eluent followed by recrystallization with MeOH and acetonitrile to yield 2-(9-chloro-2-methyl-2,3,4,5-tetrahydroazepino[4,3-b]indol-6(1H)-yl)-1-(pyridin-4-yl)ethanol. 1H NMR (CDCl3, Free base) δ (ppm): 8.5 (d, 2H), 7.4 (s, 1H), 7.3 (d, 2H), 7.19 (d, 1H), 7.05 (d, 1H), 4.85 (dd, 1H), 4.18 (m, 2H), 3.8 (d, 1H), 3.65 (d, 1H), 3.0 (m, 2H), 2.8 (m, 1H), 2.69 (m, 1H), 2.42 (s, 3H), 1.85 (m, 2H). Separation by chiral HPLC provides enantiomers II-71a-b.

Workup

  1. stirringstirring
  2. waitcontinued at RT overnight
  3. customThe progress of reaction
  4. extractionextracted with EtOAc (3×50 mL)
  5. washThe organic layer was washed with water (5×50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography
  9. customfollowed by recrystallization with MeOH and acetonitrile

Sources & evidence

ORD record
ord-a00eb1c0c8c348e8a797534f07aa8674
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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