Diethyl Ether → HCID 25115597, 화합물

HRID 1099415

반응식

HRID 1099415 반응식
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(NC(C)C)(C)C.[CH3:19][O:20][C:21]1[N:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1.C(OCC)C.FC(F)(F)S(O[C:40]1[CH:49]=[CH:48][CH:47]=[C:46]2[C:41]=1[CH2:42][C@H:43]([N:50]([CH2:58]C1C=CC=CC=1)[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:44][O:45]2)(=O)=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:58]([N:50]([CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C@H:43]1[CH2:42][C:41]2[C:46](=[CH:47][CH:48]=[CH:49][C:40]=2[C:26]2[CH:25]=[C:24]([O:27][CH3:28])[N:23]=[N:22][C:21]=2[O:20][CH3:19])[O:45][CH2:44]1)[C:8]1[CH:7]=[CH:6][CH:11]=[CH:10][CH:9]=1

참가 물질

12

반응물 7

HCID 3283Diethyl EtherHCID 7912DiisopropylamineHCID 8058HexaneHCID 783483,6-DimethoxypyridazineHCID 516892Sodium BicarbonateHCID 25053925(3S)-3-(Dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonateHCID 178418339Butyllithium

생성물 1

HCID 25115597HCID 25115597, 화합물

시약·촉매·용매 4

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

반응 조건

온도
-78 °C

실험 절차

To tetrahydrofuran (2.0 mL) cooled to −20° C. a solution of n-butyllithium 2.5 M in hexane (0.644 mL, 1.61 mmol) was added via syringe. After 5 min diisopropylamine (0.227 mL, 1.61 mmol) was added and the reaction mixture was stirred for 15 min at that temperature and then cooled down to −78° C. A solution of 3,6-dimethoxypyridazine (0.098 g, 0.7 mmol) in tetrahydrofuran (2.0 mL) was added and the reaction mixture was stirred for 1 h at −78° C. Zinc chloride 1.0 M solution in diethylether (1.610 mL, 1.61 mmol) was added and the reaction mixture was allowed to warm up to ambient temperature. A solution of (3S)-3-(Dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonate (0.368 g, 0.77 mmol) in tetrahydrofuran (2.0 mL) and tetrakis(triphenylphosphine)palladium(0) (0.032 g, 0.03 mmol) were added and the reaction mixture was heated to reflux for 16 hours. The reaction mixture was diluted with ethyl acetate and added saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate, concentrated in vacuo and purified by column chromatography using a gradient of ethyl acetate in heptane yielding 0.235 g (72%) of the desired compound as a colorless oil; 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.36 (m, 8 H), 7.19-7.25 (m, 2 H), 7.15 (t, 1 H), 6.87 (dd, 1 H), 6.81 (s, 1 H), 6.71 (dd, 1 H), 4.34 (dd, 1 H), 4.14 (s, 3 H), 4.04-4.09 (m, 1 H), 4.03 (s, 3 H), 3.69 (s, 4 H), 3.23 (br. s., 1 H), 2.29-2.99 (m, 2 H); MS (APPI/APCI) m/z 468[M+H+].

후처리

  1. additionwas added via syringe
  2. stirringthe reaction mixture was stirred for 1 h at −78° C
  3. temperatureto warm up to ambient temperature
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux for 16 hours
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography

출처 및 근거

ORD 기록
ord-30fac3552b4a4881bb997150964ba5c6
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143408B2

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