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 1404306ノート

反応式

HRID 1404306 の反応式
[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

参加物

6

反応物 4

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

生成物 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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-13025e2834ab452eb2c5edb32096cd0c
出典データセット
uspto-grants-2014_12
特許番号
US08912216B2

反応ノート

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