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 1400458노트

반응식

HRID 1400458 반응식
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

참가 물질

7

반응물 5

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

생성물 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

시약·촉매·용매 1

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

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b72b4a3c1eeb4096bf5df045a7b65f9a
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906925B2

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