Sodium Azide → HCID 71470393, compound

HRID 2408758Notes

Reaction equation

HRID 2408758 reaction equation
[C:1]([C:4]1[N:9]=[CH:8][C:7]([CH:10](OS(C)(=O)=O)[CH2:11][N:12]2[C:20]3[CH:19]=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=3[C:14]3[CH2:22][N:23]([CH3:26])[CH2:24][CH2:25][C:13]2=3)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[N-:32]=[N+:33]=[N-:34].[Na+]>CN(C=O)C.O>[N:32]([CH:10]([C:7]1[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[N:9][CH:8]=1)[CH2:11][N:12]1[C:20]2[CH:19]=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=2[C:14]2[CH2:22][N:23]([CH3:26])[CH2:24][CH2:25][C:13]1=2)=[N+:33]=[N-:34]

Participants

5

Reactant 2

HCID 33557Sodium AzideHCID 86677155HCID 86677155, compound

Product 1

HCID 71470393HCID 71470393, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Methanesulfonic acid-1-(6-carbamoyl-pyridin-3-yl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethyl ester (300 mg, 0.678 mmol) was dissolved in 5 mL DMF, and sodium azide (88 mg, 1.357 mmol) was added, and the mixture heated at 100° C. for 1 h. The reaction mixture was monitored by LCMS. After completion of reaction, the reaction mixture was cooled to RT and diluted with water (15 mL) and extracted with EtOAc (3×30 mL). The combined organic layer was washed with water (4×40 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product that was purified by reverse phase chromatography to yield 5-[1-azido-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethyl]-pyridine-2-carboxylic acid amide (135 mg). 1H NMR (CD3OD, TFA salt) δ (ppm): 8.6 (dd, 1H), 8.1 (t, 1H), 7.9 (t, 1H), 7.33 (dd, 1H), 7.26 (s, 1H), 7.06 (t, 1H), 5.3 (t, 1H), 4.7 (dd, 1H), 4.42 (dd, 1H), 4.4 (dd, 2H), 4.3 (m, 1H), 3.8 (m, 1H), 3.6 (m, 1H), 3.34 (dd, 1H), 3.1 (d, 3H), 2.4 (s, 3H). Separation by chiral HPLC provides enantiomers V-22a-b.

Workup

  1. customAfter completion of reaction
  2. temperaturethe reaction mixture was cooled to RT
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic layer was washed with water (4×40 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto obtain the crude product that
  8. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-2a8c062b4628475aab69bdb839412ab7
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

Loading…