Sodium hydride → (R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-one

HRID 1362061Notes

Reaction equation

HRID 1362061 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[CH2:10][C:11]1[C:12]([NH2:18])=[N:13][CH:14]=[C:15]([Br:17])[CH:16]=1)=O.[H-].[Na+]>CS(C)=O.O>[Br:17][C:15]1[CH:14]=[N:13][C:12]2[NH:18][C:3](=[O:2])[C@@H:5]3[N:6]([CH2:7][CH2:8][CH2:9]3)[CH2:10][C:11]=2[CH:16]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 59456924(R)-1-(2-Amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 59456939(R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-oneYield 67.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of (R)-1-(2-amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl ester (6.52 g, 20.8 mmol) in DMSO (200 mL) was treated with NaH (60% dispersion in mineral oil, 0.83 g, 20.7 mmol). After stirring at room temperature for 3 h, the mixture was stored in the freezer for 3 d. The mixture was allowed to warm to room temperature, diluted with H2O (400 mL), and extracted with EtOAc (4×200 mL). The combined organic layers were washed with H2O (3×100 mL) and brine (100 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2,/MeOH, 99:1) gave the title compound (3.94 g, 67%) as an off-white solid: MS (ESI) m/e 282 (M+H)+.

Workup

  1. waitthe mixture was stored in the freezer for 3 d
  2. temperatureto warm to room temperature
  3. extractionextracted with EtOAc (4×200 mL)
  4. washThe combined organic layers were washed with H2O (3×100 mL) and brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customPurification by flash column chromatography (silica gel, CH2Cl2,/MeOH, 99:1)

Sources & evidence

ORD record
ord-864be0fe9b824c8b8dac80f47469e436
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

Loading…