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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
ノート
印刷プレビュー

反応式

HRID 2235951 の反応式
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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ad13530f77594c45aecefba9f102edef
出典データセット
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07714004B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート