Morpholine → HCID 178515015, 화합물

HRID 2200779노트

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HRID 2200779 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][CH:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:27](=[O:28])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]3=[O:29])[CH2:15][CH2:14]2)[CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:33]1[CH2:34][CH2:35][N:30]([C:2]2[CH:11]=[C:10]3[C:5]([N:6]=[CH:7][CH:8]=[N:9]3)=[C:4]([O:12][C@@H:13]3[CH2:18][CH2:17][C@H:16]([N:19]4[C:27](=[O:28])[C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[C:20]4=[O:29])[CH2:15][CH2:14]3)[CH:3]=2)[CH2:31][CH2:32]1

참가 물질

7

반응물 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 90411339HCID 90411339, 화합물

생성물 1

HCID 178515015HCID 178515015, 화합물수율 74.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
110 °C

실험 절차

As shown in step 9-ii of Scheme 9, In a round bottom flask fitted with a condenser, a mixture of 2-[4-(7-bromoquinoxalin-5-yl)oxycyclohexyl]isoindoline-1,3-dione (6.2 g, 12.34 mmol), morpholine (1.61 g, 1.62 mL, 18.5 mmol), and Cs2CO3 (12.06 g, 37.0 mmol) in anhydrous toluene (73 mL) was treated with rac-BINAP (768.4 mg, 1.234 mmol) and Pd2(dba)3 (565 mg, 0.617 mmol). The reaction mixture was heated at 110° C. for 18 hours. After cooling to room temperature, the mixture was filtered through diatomaceous earth and concentrated under reduced pressure. The residue was triturated with Et2O and the solids collected by filtration and washed with Et2O to produce 2-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)isoindoline-1,3-dione (compound 1029, 4.2 g) as yellow solid. The filterate was concentrated under reduced pressure and purified by medium pressure silica gel chromatography (0-100% EtOAc/hexanes gradient) to produce an additional 300 mg of compound 1029: 1H-NMR (300 MHz, CDCl3) δ 8.76-8.63 (m, 2H), 7.85 (dd, J=5.4, 3.1 Hz, 2H), 7.79-7.60 (m, 2H), 7.09 (d, J=2.6 Hz, 1H), 6.99 (d, J=2.5 Hz, 1H), 5.06 (t, J=2.8 Hz, 1H), 4.27 (tt, J=12.3, 3.8 Hz, 1H), 4.02-3.85 (m, 4H), 3.49-3.27 (m, 4H), 3.03-2.75 (m, 2H), 2.37 (d, J=14.0 Hz, 2H), 1.83-1.56 (m, 4H).

후처리

  1. customAs shown in step 9-ii of Scheme 9, In a round bottom flask
  2. customfitted with a condenser
  3. temperatureAfter cooling to room temperature
  4. filtrationthe mixture was filtered through diatomaceous earth
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was triturated with Et2O
  7. filtrationthe solids collected by filtration
  8. washwashed with Et2O

출처 및 근거

ORD 기록
ord-51535908ddae49919b0298efac7a3b8e
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359380B2

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