Triethylamine → 6-(Dibenzylamino)-8-fluoroisoquinolin-1(2H)-one

HRID 735540Notes

Reaction equation

HRID 735540 reaction equation
ClC([O:4][CH2:5][CH3:6])=O.[CH2:7]([N:14]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:15]1[CH:16]=[C:17](/[CH:22]=[CH:23]/C(O)=O)C=[C:19]([F:21])[CH:20]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C([N:36](CC)CC)C.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[CH2:7]([N:14]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:15]1[CH:16]=[C:17]2[C:6](=[C:19]([F:21])[CH:20]=1)[C:5](=[O:4])[NH:36][CH:23]=[CH:22]2)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 59838035HCID 59838035, compound

Product 1

HCID 598380236-(Dibenzylamino)-8-fluoroisoquinolin-1(2H)-oneYield 83%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A solution of ethyl chloroformate (0.320 mL, 3.35 mmol) in acetone (5 mL) was added dropwise to a suspension of 19C (1.013 g, 2.80 mmol) in a mixture of acetone (30 mL) and triethylamine (0.90 mL, 6.4 mmol) at 0° C. The reaction mixture was stirred for 45 min and then a solution of sodium azide (0.350 g, 5.4 mmol) in water (8 mL) was added dropwise over 1 h. After an additional 1 h, the reaction was warmed to rt, poured into ice water, and the solid was isolated by filtration and washed with water (Do not allow the solid to dry out). (Caution: this acyl azide intermediate is potentially explosive and should be handled in small quantities behind a safety shield.) The solid was dissolved in DCM, dried (MgSO4), filtered, and the volume reduced to ˜2 mL with a stream of nitrogen. Diphenyl ether (2 mL) was added, and the crude acyl azide solution was used directly. The acyl azide solution was added slowly dropwise via addition funnel to a refluxing mixture of diphenyl ether (8.12 g) and tributylamine (2 mL), internal temperature ˜230° C. A flow of dry nitrogen was maintained through the reaction vessel to a bubbler during the reaction. Reflux was continued for an additional 1 h, after which time the majority of the solvent was removed in vacuo. The residue was cooled to room temperature and hexanes was added. The solid was collected by filtration and washed with hexanes to give 19D (0.830 g, 83%) as an off-white solid. LC-MS m/z: 359.4 (M+H)+.

Workup

  1. waitAfter an additional 1 h
  2. customthe solid was isolated by filtration
  3. washwashed with water (
  4. customto dry out)
  5. dissolution) The solid was dissolved in DCM
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. additionDiphenyl ether (2 mL) was added
  9. additionThe acyl azide solution was added slowly dropwise via addition funnel to a refluxing mixture of diphenyl ether (8.12 g) and tributylamine (2 mL), internal temperature ˜230° C
  10. temperatureA flow of dry nitrogen was maintained through the reaction vessel to a bubbler during the reaction
  11. temperatureReflux
  12. waitwas continued for an additional 1 h
  13. customafter which time the majority of the solvent was removed in vacuo
  14. temperatureThe residue was cooled to room temperature
  15. additionhexanes was added
  16. filtrationThe solid was collected by filtration
  17. washwashed with hexanes

Sources & evidence

ORD record
ord-a7b766fd8f7d4d29824705dea970753b
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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