Ethyl aluminium dichloride → (5-methoxy-2-methyl-1-(2-morpholinoethyl)-1H-indol-3-yl)(4-methylnaphthalen-1-yl)methanone

HRID 574601노트

반응식

HRID 574601 반응식
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](Cl)=[O:13])=[CH:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:21]([CH3:34])=[CH:20]2.[Cl-].[Cl-].C([Al+2])C>C(Cl)Cl>[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:21]([CH3:34])=[C:20]2[C:12]([C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:13]

참가 물질

5

반응물 3

HCID 16686341Ethyl aluminium dichlorideHCID 248874124-Methylnaphthalene-1-carbonyl chlorideHCID 667645074-(2-(5-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine

생성물 1

HCID 66764847(5-methoxy-2-methyl-1-(2-morpholinoethyl)-1H-indol-3-yl)(4-methylnaphthalen-1-yl)methanone

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-methyl-1-naphthoyl chloride (84 mg, 0.41 mmol) and 4-(2-(5-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine (120 mg, 0.44 mmol) in 8 mL CH2Cl2 at −70° C. was added dropwise ethyl aluminum dichloride (0.5 mL, 0.90 mmol, 1.8 M in toluene). The reaction mixture was allowed to slowly warm to room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and cold H2O, and the aqueous layer extracted twice with ethyl acetate. The combined organic extract was washed successively with H2O, 10% K2CO3, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 10% MeOH in CH2Cl2 to give CBX001 (107 mg, 0.24 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.37 (s, 3H), 2.42-2.55 (m, 4H), 2.66 (t, J=6.9 Hz, 2H), 2.78 (s, 3H), 3.59 (s, 3H), 3.68 (t, J=4.2 Hz, 4H), 4.17 (t, J=6.9 Hz, 2H), 6.84 (dd, J=8.8 Hz, 2.4 Hz, 1H), 6.92 (d, J=2.2 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H), 7.41-7.50 (m, 2H), 7.55 (t, J=7.2 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 8.15 (d, J=8.3 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 13.14, 20.21, 41.74, 53.90, 54.49, 55.80, 57.81, 67.29, 103.91, 110.33, 112.67, 115.61, 124.69, 125.76, 126.30, 126.59, 126.91, 128.42, 130.86, 131.35, 133.25, 136.92, 139.50, 145.98, 156.28, 193.91. MS m/z 443.4 [M+H]+.

후처리

  1. customThe reaction mixture was then partitioned between ethyl acetate and cold H2O
  2. extractionthe aqueous layer extracted twice with ethyl acetate
  3. extractionThe combined organic extract
  4. washwas washed successively with H2O, 10% K2CO3, and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified via silica gel chromatography
  9. customto give CBX001 (107 mg, 0.24 mmol)

출처 및 근거

ORD 기록
ord-5fcc62a8f9fa4aa0aa2e741242d44062
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034895B2

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