Sodium Chloride → (S)-10-[4-(3-Fluoro-propyl)-3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 131506노트

반응식

HRID 131506 반응식
Br[CH2:2][CH2:3][CH2:4][F:5].[CH3:6][O:7][CH2:8][CH2:9][C@@H:10]1[NH:15][CH2:14][CH2:13][N:12]([C:16]2[C:25]3[N:24]=[C:23]([C:26]([F:29])([F:28])[F:27])[S:22][C:21]=3[NH:20][C:19]3[CH:30]=[CH:31][CH:32]=[CH:33][C:18]=3[N:17]=2)[CH2:11]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[Cl-].[Na+]>C(O)C.O.C(OCC)(=O)C>[F:5][CH2:4][CH2:3][CH2:2][N:15]1[CH2:14][CH2:13][N:12]([C:16]2[C:25]3[N:24]=[C:23]([C:26]([F:28])([F:29])[F:27])[S:22][C:21]=3[NH:20][C:19]3[CH:30]=[CH:31][CH:32]=[CH:33][C:18]=3[N:17]=2)[CH2:11][C@@H:10]1[CH2:9][CH2:8][O:7][CH3:6]

참가 물질

9

반응물 5

HCID 5234Sodium ChlorideHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 67699Propane, 1-bromo-3-fluoro-HCID 135457486(S)-10-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

생성물 1

HCID 136090394(S)-10-[4-(3-Fluoro-propyl)-3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

Add 1-bromo-3-fluoropropane (0.14 mL, 1.52 mmol) to a slurry of (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.52 g, 1.26 mmol), powdered potassium carbonate (0.87 g, 6.32 mmol), and sodium iodide (0.95 g, 6.32 mmol) in absolute ethanol (7.8 mL) and heat to reflux. After an overnight period, cool, add saturated aqueous sodium chloride and ethyl acetate, and add deionized water to dissolve precipitated salt that formed during the extraction. Extract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate), filter, and concentrate organics under reduced pressure to an oil (0.564 g). Purify the oil by flash chromatography, eluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%) to give the title compound: mass spectrum (APCI, m/e): 472 (M+1); NMR (1H, 300 MHz, DMSO-d6): δ 8.47 (s, 1H), 6.96-6.82 (m, 3H), 6.71 (m, 1H), 4.55 (td, 2H, 2J(H,F)=48 Hz, 3J(H,H)=5.7 Hz), 3.47 (br. m, 3H), 3.31-3.18 (m, 3H), 3.15 (s, 3H), 2.70 (m, 2H), 2.55 (br. m, 1H), 2.38 (m, 2H), 1.86-1.67 (in, 3H), 1.61 (m, 1H).

후처리

  1. temperatureheat to reflux
  2. temperaturecool
  3. dissolutionto dissolve
  4. customprecipitated salt
  5. customthat formed during the extraction
  6. dry with materialExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate organics under reduced pressure to an oil (0.564 g)
  9. customPurify the oil by flash chromatography
  10. washeluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%)

출처 및 근거

ORD 기록
ord-2c1ebb5ec1194163a73552fcb30b856f
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384934B2

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