Water → HCID 71008148, compound

HRID 1630657Notes

Reaction equation

HRID 1630657 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-4eb3c75f905f4dd09a23302288ff98f5
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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