Potassium Phosphate, Tribasic → (E)-6-fluoro-2-methyl-5-(2-(6-methylpyridin-3-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400467ノート

反応式

HRID 1400467 の反応式
[F:1][C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:37]=[CH:38][C:39]([CH3:42])=[N:40][CH:41]=1)[CH3:35]>CN(C=O)C.[Cu]I>[F:1][C:2]1[C:10]2[N:9](/[CH:33]=[C:34](/[C:36]3[CH:41]=[N:40][C:39]([CH3:42])=[CH:38][CH:37]=3)\[CH3:35])[C:8]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 510437126-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleHCID 866447585-(2-Bromo-1-methyl-vinyl)-2-methyl-pyridine

生成物 1

HCID 53373127(E)-6-fluoro-2-methyl-5-(2-(6-methylpyridin-3-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

実験手順

6-Fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (203 mg, 0.8 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (19 mg, 0.10 mmol), L-proline (23 mg, 0.20 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 5-(1-Bromoprop-1-en-2-yl)-2-methylpyridine (212 mg, 1 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 80° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh). The product was further purified by HPLC. 1H NMR (CDCl3, TFA salt) δ (ppm): 9.10 (s, 1H), 8.30 (d, 1H), 7.62 (m, 1H), 7.22 (s, 1H), 7.18 (d, 1H), 7.10 (m, 1H), 6.95 (m, 1H), 5.80 (m, 1H), 4.10 (m, 1H), 3.90 (m, 1H), 3.30 (m, 2H), 3.05 (s, 3H), 2.95 (m, 1H), 2.80 (s, 3H), 2.0 (s, 3H).

後処理

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 80° C. (
  3. temperatureprolonged heating in some cases
  4. customDMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)
  8. customThe product was further purified by HPLC

出典と根拠

ORDレコード
ord-f9ebb90bafd14396a4f206e786274b9c
出典データセット
uspto-grants-2014_12
特許番号
US08906925B2

反応ノート

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