Triethylamine → 7-(1-Azidoethyl)-5-chloro-8-(3-fluorophenyl)isoquinoline

HRID 1192593Notes

Reaction equation

HRID 1192593 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([CH:12](O)[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.C(N(CC)CC)C.CS(Cl)(=O)=O.CS(OC(C1C(C2C=CC=C(F)C=2)=C2C(C=CN=C2)=C(Cl)C=1)C)(=O)=O.[N-:59]=[N+:60]=[N-:61].[Na+]>C(Cl)Cl.CN(C)C=O>[N:59]([CH:12]([C:10]1[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]([CH:4]=[CH:5][N:6]=[CH:7]2)=[C:2]([Cl:1])[CH:11]=1)[CH3:13])=[N+:60]=[N-:61]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 583686851-[5-Chloro-8-(3-fluorophenyl)isoquinolin-7-yl]ethanolHCID 866561801-[5-Chloro-8-(3-fluorophenyl)isoquinolin-7-yl]ethyl methanesulfonate

Product 1

HCID 583684257-(1-Azidoethyl)-5-chloro-8-(3-fluorophenyl)isoquinolineYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 1-[5-chloro-8-(3-fluorophenyl)isoquinolin-7-yl]ethanol (0.100 g, 0.331 mmol) in methylene chloride (0.6 mL) was added triethylamine (0.092 mL, 0.66 mmol) followed by methanesulfonyl chloride (0.038 mL, 0.50 mmol) at 0° C. The reaction was stirred at room temperature for 30 minutes, then diluted with dichloromethane and washed with water. The organic layers were dried over magnesium sulfate and concentrated to dryness under reduced pressure. The resulting sulfonate was used in the next step. LCMS (M+H)+380.1. To the this crude 1-[5-chloro-8-(3-fluorophenyl)isoquinolin-7-yl]ethyl methanesulfonate in N,N-dimethylformamide (0.6 mL) was added sodium azide (0.11 g, 1.6 mmol). The reaction was stirred at room temperature for 1 hour, then quenched with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated to dryness to provide crude desired azide (0.105 mg, 97%). LCMS calculated for C17H13ClFN4 (M+H)+: m/z=327.1; Found: 327.1.

Workup

  1. washwashed with water
  2. dry with materialThe organic layers were dried over magnesium sulfate
  3. concentrationconcentrated to dryness under reduced pressure
  4. stirringThe reaction was stirred at room temperature for 1 hour
  5. customquenched with water
  6. extractionextracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-94c27e0dd4c7490ebafd7046483c7d5e
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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