Toluene → 3-Methoxy-5-[4-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-3',5'-bis(trifluoromethyl)biphenyl-2-yl]pyridine

HRID 383775

反応式

HRID 383775 の反応式
Br[C:2]1[CH:7]=[C:6]([C:8]([N:10]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1.[CH3:35][O:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCO.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]>[CH3:35][O:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41]([C:2]2[CH:7]=[C:6]([C:8]([N:10]3[CH2:14][CH2:13][CH:12]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH2:11]3)=[O:9])[CH:5]=[CH:4][C:3]=2[C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH:42]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 866577533-(1-{[2-Bromo-3',5'-bis(trifluoromethyl)biphenyl-4-yl]carbonyl}pyrrolidin-3-yl)pyridine

生成物 1

HCID 866577523-Methoxy-5-[4-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-3',5'-bis(trifluoromethyl)biphenyl-2-yl]pyridine

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒

反応条件

温度
125 °C

実験手順

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.7 mg, 0.019 mmol) was added to a solution of 3b (51.0 mg, 0.094 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (24.3 mg, 0.103 mmol) and sodium carbonate (94.0 μL, of a 2.0 M aqueous solution, 0.188 mmol) in EtOH:toluene (1.25 mL of an 80:20 mixture, respectively) at rt. The resulting solution was heated to 125° C. in a sealed microwave vial for 12 min. After cooling to rt, the reaction mixture was filtered through a short column of Celite®, eluting with EtOAc. The filtrate was washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier), followed by lyophilization of the purified fractions afforded the title compound 3c. m/z (ES) 572 (MH)+.

後処理

  1. customat rt
  2. temperatureAfter cooling to rt
  3. filtrationthe reaction mixture was filtered through a short column of Celite®
  4. washeluting with EtOAc
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier)

出典と根拠

ORDレコード
ord-375568f3d46d434fbe85ed83ce9dcafc
出典データセット
uspto-grants-2013_02
特許番号
US08367679B2

関連ノート

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