Dichloromethane → 5-{4-[6,7-Bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-3-nitropyridin-2-amine

HRID 241209

반응식

HRID 241209 반응식
[N+:1]([C:4]1[C:5]([NH2:19])=[N:6][CH:7]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:9]=1)([O-:3])=[O:2].[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[N:28]=[CH:27][CH:26]=[C:25]2[N:34]1[CH2:40][C:39]2[CH:41]=[C:42](Br)[CH:43]=[CH:44][C:38]=2[O:37][CH2:36][CH2:35]1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[N:28]=[CH:27][CH:26]=[C:25]2[N:34]1[CH2:40][C:39]2[CH:41]=[C:42]([C:8]3[CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[C:5]([NH2:19])=[N:6][CH:7]=3)[CH:43]=[CH:44][C:38]=2[O:37][CH2:36][CH2:35]1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 467380093-Nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 668199804-[6,7-Bis(methyloxy)quinolin-4-yl]-7-bromo-2,3,4,5-tetrahydro-1,4-benzoxazepine

생성물 1

HCID 668204025-{4-[6,7-Bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-3-nitropyridin-2-amine수율 76%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
93 °C

실험 절차

A mixture of commercially available 3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (125 mg, 0.47 mmol), 4-[6,7-bis(methyloxy)quinolin-4-yl]-7-bromo-2,3,4,5-tetrahydro-1,4-benzoxazepine (155 mg, 0.47 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (34 mg, 0.05 mmol), cesium carbonate (300 mg, 2.4 mmol) in 1,4-dioxane (20 mL) and water (2 mL) was degassed with nitrogen for 5 minutes and then stirred at 93° C. for 18 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (80 mL) then filtered through a celite bed. The filtrate was washed with brine (2×50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel flash chromatography (0 to 10% methanol-dichloromethane) to give 5-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-3-nitropyridin-2-amine (135 mg, 76% yield); MS (EI) for C25H23N5O5: 474 (MH+).

후처리

  1. customwas degassed with nitrogen for 5 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (80 mL)
  4. filtrationthen filtered through a celite bed
  5. washThe filtrate was washed with brine (2×50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel flash chromatography (0 to 10% methanol-dichloromethane)

출처 및 근거

ORD 기록
ord-fe281c686921448794c918301016aa00
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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