Dimethylformamide → (E)-2-methyl-5-(2-(6-methylpyridin-3-yl)prop-1-enyl)-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401533ノート

反応式

HRID 1401533 の反応式
CN1CCC2NC3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11]C=3C=2C1.[NH:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21](O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:36]=[C:37]([C:39]1[CH:40]=[CH:41][C:42]([CH3:45])=[N:43][CH:44]=1)[CH3:38].[CH3:46][N:47]([CH:49]=O)[CH3:48]>[Cu]I>[CH3:46][N:47]1[CH2:49][CH2:21][C:20]2[N:19](/[CH:36]=[C:37](/[C:39]3[CH:44]=[N:43][C:42]([CH3:45])=[CH:41][CH:40]=3)\[CH3:38])[C:26]3[CH:11]=[C:10]([C:13]([F:14])([F:16])[F:15])[CH:9]=[CH:8][C:25]=3[C:24]=2[CH2:48]1

参加物

7

反応物 5

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67311103HCID 67311103、化合物HCID 866447585-(2-Bromo-1-methyl-vinyl)-2-methyl-pyridine

生成物 1

HCID 53372991(E)-2-methyl-5-(2-(6-methylpyridin-3-yl)prop-1-enyl)-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

試薬・触媒・溶媒 1

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

実験手順

2-Methyl-8-(trifluoromethyl)-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 85° 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) eluting with 0-5% MeOH-DCM. The product was further purified by HPLC. 1H NMR (CDCl3, TFA salt) δ (ppm): 9.10 (s, 1H), 8.30 (d, 1H), 7.65 (d, 1H), 7.55 (d, 1H), 7.45 (d, 1H), 7.40 (s, 1H), 7.10 (s, 1H), 4.80 (m, 1H), 4.20 (m, 1H), 3.90 (m, 1H), 3.40 (m, 2H), 3.10 (s, 3H), 3.0 (m, 1H), 2.82 (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 85° 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. washeluting with 0-5% MeOH-DCM
  9. customThe product was further purified by HPLC

出典と根拠

ORDレコード
ord-16366b74cbc54fd580ee3b3fab0514c6
出典データセット
uspto-grants-2014_12
特許番号
US08907097B2

反応ノート

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