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Cesium carbonate → (s)-n-(1-(5-Chloropyridin-2-yl)-1-(3-ethoxy-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

HRID 1365496
ノート
印刷プレビュー

反応式

HRID 1365496 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:24][C:25](=[O:37])[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([C:33]([F:36])([F:35])[F:34])[CH:27]=2)([C:16]2[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[C:45]([C:48](OCC)=O)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:24][C:25](=[O:37])[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([C:33]([F:34])([F:36])[F:35])[CH:27]=2)([C:16]2[CH:17]=[C:18]([F:23])[CH:19]=[C:20]([O:22][CH2:45][CH3:48])[CH:21]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=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

6

反応物 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 2737200Ethyl difluoro(iodo)acetateHCID 58920056(S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

生成物 1

HCID 58921033(s)-n-(1-(5-Chloropyridin-2-yl)-1-(3-ethoxy-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide
収率 7.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution of (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (32 mg, 0.06 mmol, prepared as described in Procedure 14) in DMF (0.5 mL) was added Cs2CO3 (39 mg, 0.12) and ICF2CO2Et (28 mg, 0.12 mmol). The mixture was heated at 60° C. for 3 days. NaHCO3 was added. It was extracted with CH2Cl2. The organic layer was washed with 10% citric acid, brine, dried over MgSO4, concentrated and the crude mixture was purified by preparative HPLC (phenominex C18 column, 21×100 mm, 5 μ) using MeOH/H2O (0.1% TFA) to give two products, (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-ethoxy-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (2.5 mg, 7% yield) as a pale yellow solid, LCMS: 4.38 min [M+1] 561.44 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 1.33-1.40 (m, J=6.88, Hz, 3 H), 3.61 (d, J=12.88 Hz, 1 H), 3.93-4.00 (m, 2 H), 4.54 (d, J=12.88 Hz, 1 H), 6.49-6.56 (m, 3 H), 6.76 (dt, J=9.85, 1.89 Hz, 1 H), 6.84 (s, 1 H), 7.02 (t, J=7.45 Hz, 2 H), 7.11 (t, J=7.33 Hz, 1 H), 7.22-7.31 (m, 3 H), 7.70 (dd, J=8.59, 2.27 Hz, 1 H), 7.85-7.90 (m, 1 H), 8.03 (dd, J=6.82, 2.02 Hz, 1 H), 8.32 (d, J=2.53 Hz, 1 H), 9.11 (s, 1 H), and (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-(difluoromethoxy)-5-fluorophenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (3 mg, 7% yield) as a pale yellow foam, LCMS: 4.28 min [M+1] 583.32 (4 min gradient, MeOH/H2O 0.1% TFA); 1 H NMR (400 MHz, CDCl3) δ ppm 3.61 (d, J=12.88 Hz, 1 H), 4.54 (d, J=12.88 Hz, 1 H), 6.51 (m, 3 H), 6.76-6.83 (m, 1 H), 7.00-7.08 (m, 4 H), 7.13 (t, J=7.45 Hz, 1 H), 7.20-7.29 (m, 2 H), 7.74 (dd, J=8.59, 2.27 Hz, 1 H), 7.87 (ddd, J=8.46, 4.67, 2.27 Hz, 1 H), 8.02 (dd, J=6.69, 1.89 Hz, 1 H), 8.35 (d, J=2.27 Hz, 1 H), 9.11 (s, 1 H).

後処理

  1. extractionIt was extracted with CH2Cl2
  2. washThe organic layer was washed with 10% citric acid, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customthe crude mixture was purified by preparative HPLC (phenominex C18 column, 21×100 mm, 5 μ)

出典と根拠

ORDレコード
ord-3738b541eaa145e38fa8c0108cc4e9ec
出典データセット
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07888376B2

反応ノート

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