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Potassium Phosphate, Tribasic → 2-[4-(1-Methyl-1H-indol-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 474149
ノート
印刷プレビュー

反応式

HRID 474149 の反応式
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1B(O)O.I[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:24][C@@H:25]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:29][N:28]=2)[CH3:26])=[O:23])=[CH:17][CH:16]=1.ON1C2N=CC=CC=2N=N1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.CCOC(C)=O.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].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O1CCOCC1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:15]1[CH:16]=[CH:17][C:18]([CH2:21][C:22]([NH:24][C@@H:25]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([F:38])([F:36])[F:37])=[CH:29][N:28]=2)[CH3:26])=[O:23])=[CH:19][CH:20]=1
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

10

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 181649HOAtHCID 22733820(1-Methyl-1H-indol-2-yl)boronic acidHCID 668924152-(4-iodophenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

生成物 1

HCID 426100132-[4-(1-Methyl-1H-indol-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide収率 79.2%

試薬・触媒・溶媒 5

HCID 75806Tricyclohexylphosphine触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

To a mixture of (1-methyl-1H-indol-2-yl)boronic acid (37.7 mg mg, 0.215 mmol), 2-(4-iodophenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide (50.0 mg, 0.108 mmol), tricyclohexylphosphine (0.7 mg, 0.003 mmol), 1-hydroxy-7-azabenzotriazole (101 mg, 0.744 mmol) and Pd2(dba)3 (1 mg, 0.001 mmol) were added dioxane (0.4 mL) and a solution of K3PO4 in H2O (0.2 mL, 1.27 M). The resulting solution was heated in microwave at 150° C. for 0.5 hr. The reaction was completed and diluted with EtOAc. The water later was removed. The remaining organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by reverse-phase HPLC to give the product as a TFA salt (40 mg, 79%). 1H NMR (CDCl3, 400 MHz) δ 8.22 (dd, J=0.8, 2.8 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.49 (dd, J=2.0, 6.4 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.37 (d, J=6.4, 1H), 7.27-7.19 (m, 2H), 7.14 (t, J=8.0 Hz, 1H), 6.80 (d, J=7.2 Hz, 1H), 6.56 (s, 1H), 5.14 (quintet, J=7.2 Hz, 1H), 4.38 (q, J=8.0 Hz, 2H), 3.75 (s, 3H), 3.65 (s, 2H), 1.44 (d, J=6.8 Hz, 3H); HRMS (ES) [M+1]+ calcd for C26H25F3N3O2: 468.1893, Found: 468.1889. FLIPR alpha1I IP=36 nM.

後処理

  1. customThe water later was removed
  2. dry with materialThe remaining organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse-phase HPLC

出典と根拠

ORDレコード
ord-21504919dc03448da312f4dfeab10bd0
出典データセット
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08637513B2

反応ノート

読み込み中…

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