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Dichloromethane → ethyl ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235951
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HRID 2235951 반응식
Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)[C:5]([CH3:29])=[CH:4][N:3]=1.[CH2:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[CH3:31].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=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].O1CCOCC1.C1(C)C=CC=CC=1>[CH2:30]([C:32]1[CH:37]=[CH:36][C:35]([C:2]2[N:7]=[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]4)[C:5]([CH3:29])=[CH:4][N:3]=2)=[CH:34][CH:33]=1)[CH3:31]
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HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2734352Boronic acid, (4-ethylphenyl)-HCID 59300440ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

생성물 1

HCID 59300499ethyl ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate
수율 59%

시약·촉매·용매 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
75 °C

실험 절차

To a mixture of toluene (12 mL) and 1,4-dioxane (2.5 mL) were added ethyl ((1S)-5-{3-[(2chloro-5-methyl-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 342, 205 mg, 0.49 mmol), 4-ethylphenyl boronic acid (294 mg, 1.96 mmol), and PdCl2(dppf).CH2Cl2 (35.9 mg, 0.05 mmol). A flow of argon was passed through the reaction mixture for 30 min, then Na2CO3 (2.45 mL, 4.91 mmol, 2 M aqueous solution) was added, and the reaction was stirred at 75° C. for 18 h. After cooling to rt, the reaction mixture was diluted with EtOAc, and washed with a saturated aqueous solution of NaHCO3. The organic layer was then dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc) to provide the product (140 mg, 59%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.26-1.32 (m, 6H), 1.73-1.80 (m, 1H), 2.16-2.19 (m, 2H), 2.33 (s, 3H), 2.35-2.42 (m, 2H), 2.67-2.88 (m, 5H), 3.22 (s, 3H), 3.51-3.55 (m, 1H), 3.79 (t, 2H), 4.00 (t, 2H), 4.19 (q, 2H), 6.69 (d, 1H), 6.75 (s, 1H), 7.04 (d, 1H), 7.26 (d, 2H), 8.08 (s, 1H), 8.30 (d, 2H).

후처리

  1. temperatureAfter cooling to rt
  2. washwashed with a saturated aqueous solution of NaHCO3
  3. dry with materialThe organic layer was then dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-ad13530f77594c45aecefba9f102edef
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07714004B2

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