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

HRID 2235961
ノート
印刷プレビュー

反応式

HRID 2235961 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[CH2:12]([O:14][C:15](=[O:40])[CH2:16][C@H:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH2:27][CH2:28][CH2:29][N:30]([C:32]3[C:37](Cl)=[CH:36][N:35]=[C:34](Cl)[N:33]=3)[CH3:31])=[CH:23][CH:24]=2)[CH2:19][CH2:18]1)[CH3:13].C(Cl)Cl.[C:44](=[O:47])([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.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]>[CH2:12]([O:14][C:15](=[O:40])[CH2:16][C@H:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH2:27][CH2:28][CH2:29][N:30]([C:32]3[C:37]([C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)=[CH:36][N:35]=[C:34]([C:3]4[CH:8]=[CH:7][C:6]([O:47][CH3:44])=[CH:5][CH:4]=4)[N:33]=3)[CH3:31])=[CH:23][CH:24]=2)[CH2:19][CH2:18]1)[CH3:13]
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

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 59300554ethyl ((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

生成物 1

HCID 59300448ethyl ((1S)-5-{3-[[2,5-bis(4-methoxyphenyl)-4-pyrimidinyl](methy)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate収率 64.8%

試薬・触媒・溶媒 3

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

反応条件

温度
75 °C

実験手順

To a mixture of 4-methoxyphenylboronic acid (142 mg, 0.913 mmol) and ethyl((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 442, 100 mg, 0.228 mmol ) in toluene (5 mL) and 1,4-dioxane (1.25 mL) was added PdCl2(dppf).CH2Cl2(19 mg, 0.023 mmol). The mixture was purged with argon for 15 min after which sodium carbonate (1.2 mL, 2.40 mmol, 2 M aqueous solution) was added. The mixture was stirred at 75° C. for 18 h, cooled to rt, and then washed with a saturated sodium bicarbonate solution. The organic layer was separated from the mixture and the aqueous phase extracted with EtOAc. The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (1:4 EtOAc/Hexanes) to give (86 mg, 64%) of the desired product. 1H NMR (400 MHz, CDCl3): δ 1.30 (t, 3H), 1.70-1.80 (m, 1H), 2.15-2.20 (m, 2H), 2.28-2.45 (m, 2H), 2.70 (dd, 1H), 2.72-2.90 (m, 2H), 2.80 (s, 3H), 3.45-3.55 (m, 1H), 3.75 (t, 2H), 3.85 (s, 3H), 3.92 (s, 3H), 3.95 (t, 2H), 4.20 (q, 2H), 6.65 (d, 1H), 6.7 (s, 1H), 6.9 (d, 2H), 6.95 (d, 2H), 7.05 (s, 1H), 7.32 (d, 2H), 8.15 (s, 1H), 8.40 (d, 2H).

後処理

  1. additionwas added
  2. temperaturecooled to rt
  3. washwashed with a saturated sodium bicarbonate solution
  4. customThe organic layer was separated from the mixture
  5. extractionthe aqueous phase extracted with EtOAc
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography (1:4 EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-366bc65cea85438fa2bed5953d8d6753
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

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