Sodium Carbonate → 4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 76048ノート

反応式

HRID 76048 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:37]2[CH:38]=[N:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=2)=[N:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:30]3[CH:35]=[N:34][C:33]([NH:36][C:37]4[CH:38]=[N:39][C:40]([C:43]([F:45])([F:46])[F:44])=[CH:41][CH:42]=4)=[CH:32][CH:31]=3)=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 53629760tert-Butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine-1-carboxylateHCID 66615754(5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

生成物 1

HCID 666159164-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperidine-1 carboxylic acid tert-butyl ester (1.56 g, 4.1 mmol) and (5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine (1.28 g, 4.0 mmol) were dissolved in DME (8 mL) in a pressure vessel, and to the solution was added PdCl2dppf (100 mg, 0.12 mmol) and Na2CO3 (2.0M, 4.0 mL, 8.1 mmol). The mixture was sparged with nitrogen for 10 minutes, then the vessel was sealed and stirred at 80° C. for 18 hours. The mixture was partitioned between EtOAc and saturated aqueous NH4Cl, 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 (10-50%) to obtain the target compound as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (br. s., 2H) 1.42 (s, 9H) 1.52 (qd, J=12.63, 4.55 Hz, 2H) 1.77 (m, 2H) 2.66-2.76 (m, 1H) 4.09 (m, 2H) 7.03 (d, J=8.59 Hz, 1H) 7.34 (d, J=8.34 Hz, 2H) 7.60 (d, J=8.08 Hz, 2H) 7.79 (d, J=8.84 Hz, 1H) 7.99 (dd, J=8.72, 2.65 Hz, 1H) 8.56 (d, J=2.53 Hz, 1H) 8.91 (d, J=2.53 Hz, 1H) 9.87 (s, 1H); MS (M+H)+499.3.

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 saturated aqueous NH4Cl
  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 (10-50%)

出典と根拠

ORDレコード
ord-123d9f0f95a6444d9e601ce849e30fc3
出典データセット
uspto-grants-2014_09
特許番号
US08835451B2

反応ノート

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