Sodium Iodide → HCID 58368464, compound

HRID 1192725Notes

Reaction equation

HRID 1192725 reaction equation
[N:1]([C@H:4]([C:6]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[C:14]2[C:9]([CH:10]=[CH:11][N:12]=[N:13]2)=[C:8]([Cl:23])[CH:7]=1)[CH3:5])=[N+]=[N-].[I-].[Na+].Cl[Si](C)(C)C.S([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>CO.O>[Cl:23][C:8]1[CH:7]=[C:6]([C@@H:4]([NH2:1])[CH3:5])[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[C:14]2[C:9]=1[CH:10]=[CH:11][N:12]=[N:13]2

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 14798Sodium HydroxideHCID 24437Sodium SulfiteHCID 58368459HCID 58368459, compound

Product 1

HCID 58368464HCID 58368464, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of 7-[(1S)-1-azidoethyl]-5-chloro-8-(3-fluorophenyl)cinnoline (48 g, 150 mmol) in methanol (430 mL) was treated with sodium iodide (130 g, 880 mmol) and stirred at room temperature for 10 minutes. The reaction mixture was cooled with a water bath. The reaction mixture was treated with chlorotrimethylsilane (110 mL, 880 mmol) dropwise over 20 minutes while maintaining the internal temperature at 28-35° C. The reaction mixture turned dark red and the stirring was continued for 26 min. After 42 min, the reaction mixture was treated with a solution of sodium sulfite (130 g, 1.0 mol) in water (430 mL). The dark red color of the solution faded and gave a yellow suspension. The reaction mixture was stirred for 30 minutes and then concentrated under reduced pressure to remove the methanol. The mixture was adjusted to pH>11 with 3 N NaOH solution and extracted with dichloromethane. The pH of the solution changed during the work-up, potentially due to the slow hydrolysis of TMSCl. The pH needed to be checked regularly and basified to pH>11 by addition of 3 N NaOH. The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the desired product (43 g, 96%) as a solid. LCMS for C16H14ClFN3 (M+H)+: m/z=302.1; Found: 302.0; 1H NMR (300 MHz, DMSO-d6): δ 9.47 (d, J=5.9 Hz, 1H), 8.41 (d, J=1.9 Hz, 1H), 8.29 (d, J=5.9 Hz, 1H), 7.59-7.49 (m, 1H), 7.34-7.14 (m, 3H), 4.04-3.95 (m, 1H), 2.22 (br s, 2H), 1.21-1.16 (m, 3H).

Workup

  1. temperatureThe reaction mixture was cooled with a water bath
  2. temperaturewhile maintaining the internal temperature at 28-35° C
  3. waitthe stirring was continued for 26 min
  4. waitAfter 42 min
  5. customgave a yellow suspension
  6. stirringThe reaction mixture was stirred for 30 minutes
  7. concentrationconcentrated under reduced pressure
  8. customto remove the methanol
  9. extractionextracted with dichloromethane
  10. customThe pH of the solution changed during the work-up, potentially due to the slow hydrolysis of TMSCl
  11. washThe combined organic extracts were washed with brine (50 mL)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-c049fd91214a458698e9537b14799408
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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