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Sodium Carbonate → (4-{4-[6-(2-Methyl-6-trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester

HRID 1404238
ノート
印刷プレビュー

反応式

HRID 1404238 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[C:10]([CH3:19])=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=2)=[N:6][CH:7]=1.[CH3:20][O:21][C:22](=[O:45])[CH2:23][CH:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)[CH2:26][CH2:25]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:20][O:21][C:22](=[O:45])[CH2:23][CH:24]1[CH2:25][CH2:26][CH:27]([C:30]2[CH:31]=[CH:32][C:33]([C:2]3[CH:7]=[N:6][C:5]([NH:8][C:9]4[C:10]([CH3:19])=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=4)=[CH:4][CH:3]=3)=[CH:34][CH:35]=2)[CH2:28][CH2:29]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

5

反応物 3

HCID 10340Sodium CarbonateHCID 57992171Methyl 2-(trans-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclohexyl)acetateHCID 66615910(5-Bromo-pyridin-2-yl)-(2-methyl-6-trifluoromethyl-pyridin-3-yl)-amine

生成物 1

HCID 66615758(4-{4-[6-(2-Methyl-6-trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester

試薬・触媒・溶媒 1

HCID 8071
1,2-Dimethoxyethane
溶媒

反応条件

温度
80 °C

実験手順

(5-Bromo-pyridin-2-yl)-(2-methyl-6-trifluoromethyl-pyridin-3-yl)-amine (290 mg, 0.87 mmol) and {4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester (312 mg, 0.87 mmol) were dissolved in anhydrous DME (3 mL) in a pressure vessel. PdCl2dppf (21 mg, 0.026 mmol) was added, followed by aqueous sodium carbonate (2M, 0.870 mL, 1.74 mmol). The mixture was sparged with nitrogen for 10 minutes, then the vessel was sealed and heated at 80° C. for 18 hours. The mixture was partitioned between EtOAc and water, washed with brine, dried with magnesium sulfate, filtered, and concentrated via rotary evaporation. The crude material was purified via column chromatography on silica gel, eluting with a gradient of EtOAc/hexanes (7-50%) to obtain the target compound as a solid: 1H NMR (400 MHz, DMSO-d6) ppm 1.08-1.21 (m, 2 H) 1.50 (td, J=12.44, 10.23 Hz, 2 H) 1.81 (m, 4 H) 2.25 (d, J=6.57 Hz, 2 H) 2.59 (s, 3 H) 3.60 (s, 3 H) 7.22 (d, J=8.59 Hz, 1 H) 7.31 (d, J=8.34 Hz, 2 H) 7.57 (d, J=8.34 Hz, 2 H) 7.66 (d, J=8.59 Hz, 1 H) 7.97 (dd, J=8.59, 2.53 Hz, 1 H) 8.48 (d, J=2.53 Hz, 1 H) 8.64 (s, 1 H) 8.66 (d, J=8.34 Hz, 1 H); MS (M+H)+ 484.3.

後処理

  1. customThe mixture was sparged with nitrogen for 10 minutes
  2. customthe vessel was sealed
  3. customThe mixture was partitioned between EtOAc and water
  4. washwashed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation
  8. customThe crude material was purified via column chromatography on silica gel
  9. washeluting with a gradient of EtOAc/hexanes (7-50%)

出典と根拠

ORDレコード
ord-36bec9451f694d549fd8626833bef044
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08912208B2

反応ノート

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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