Triethylamine → 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(2-morpholin-4-yl-ethyl)-1H-[1,2,3]triazol-4-yl]pyridin-3-yl}-[1,8]naphthyridine

HRID 1914956Notes

Reaction equation

HRID 1914956 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C:8]2[CH:17]=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([C:24]#[C:25][Si](CC)(CC)CC)[CH:23]=3)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(N(CC)CC)C.[N:59]([CH2:62][CH2:63][N:64]1[CH2:69][CH2:68][O:67][CH2:66][CH2:65]1)=[N+:60]=[N-:61]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C:8]2[CH:17]=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([C:24]4[N:61]=[N:60][N:59]([CH2:62][CH2:63][N:64]5[CH2:65][CH2:66][O:67][CH2:68][CH2:69]5)[CH:25]=4)[CH:23]=3)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 27370154-(2-Azidoethyl)morpholineHCID 673663752-(5-Chloro-2-fluoro-phenyl)-4-(5-triethylsilanylethynyl-pyridin-3-yl)-[1,8]naphthyridine

Product 1

HCID 673650672-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(2-morpholin-4-yl-ethyl)-1H-[1,2,3]triazol-4-yl]pyridin-3-yl}-[1,8]naphthyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 471 mg (0.994 mmol) 2-(5-chloro-2-fluoro-phenyl)-4-(5-triethylsilanylethynyl-pyridin-3-yl)-[1,8]naphthyridine in 6 ml THF was treated with 1.19 ml of a 1 M solution of tetra-n-butylammonium fluoride in THF and stirred for 1 hour at room temperature. Then 276 μl (1.99 mmol) triethylamine, 190 mg (1.21 mmol) 4-(2-azido-ethyl)-morpholine and 9.5 mg (0.05 mmol) cuprous iodide were added. The reaction mixture was stirred for 66 hours at 70° C. The reaction mixture was cooled to room temperature and partitioned between ethylacetate and brine. The organic phase was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(2-morpholin-4-yl-ethyl)-1H-[1,2,3]triazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine as colourless solid; HPLC-MS: 1.50 min, [M+H] 516.

Workup

  1. stirringThe reaction mixture was stirred for 66 hours at 70° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between ethylacetate and brine
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated
  6. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-929b4382f1f04652adb42e4f9eca59f6
Source dataset
uspto-grants-2013_12
Patent number
US08614226B2

Reaction notes

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