Water → HCID 71008148, compound

HRID 1469594Notes

Reaction equation

HRID 1469594 reaction equation
CS(O[CH:6]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH2:7][N:8]1[C:16]2[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[C:10]2[CH:18]3[N:22]([CH2:23][CH2:24][C:9]1=2)[CH2:21][CH2:20][CH2:19]3)(=O)=O.[N-:32]=[N+:33]=[N-:34].[Na+].O>CN(C)C=O>[N:32]([CH:6]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH2:7][N:8]1[C:16]2[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[C:10]2[CH:18]3[N:22]([CH2:23][CH2:24][C:9]1=2)[CH2:21][CH2:20][CH2:19]3)=[N+:33]=[N-:34]

Participants

5

Reactant 3

HCID 962WaterHCID 33557Sodium AzideHCID 86677156HCID 86677156, compound

Product 1

HCID 71008148HCID 71008148, compoundYield 7.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(4-fluorophenyl)-2-(10-methyl-2,3,5,6-tetrahydro-1H-indolizino[7,8-b]indol-7(11cH)-yl)ethyl methanesulfonate (400 mg, 0.9 mmol) and sodium azide (88 mg, 1.3 mmol) in dimethylformamide (10 mL) was stirred at RT for 18 h. The reaction mixture was diluted with ice cooled water (100 mL) and extracted with EtOAc (100 mL). The organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product that was purified by reverse phase HPLC to yield 7-(2-azido-2-(4-fluorophenyl)ethyl)-10-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (25 mg). 1H NMR (CD3OD, freebase) δ (ppm): 7.32 (m, 3H), 7.26 (s, 1H), 7.13 (m, 2H), 7.09 (d, 1H), 5.09 (t, 1H), 4.8 (m, 1H), 4.32 (m, 2H), 3.44 (m, 2H), 3.3 (m, 1H), 3.1 (m, 1H), 3.0 (d, 1H), 2.8 (m, 1H), 2.6 (m, 1H), 2.4 (s, 3H), 2.18 (m, 2H), 2.0 (m, 1H). Separation by chiral HPLC provides diastereomers V-23a-d.

Workup

  1. additionThe reaction mixture was diluted with ice
  2. extractionextracted with EtOAc (100 mL)
  3. washThe organic layer was washed with water (5×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto obtain the crude product that
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3bf20da9165d4d7ebbeb7f9ac035d433
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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