2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide

HRID 1408142ノート

反応式

HRID 1408142 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:20])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[CH:5]=[CH:4][N:3]=1.[N:21]1([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:28]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:33][C:30]1[CH:29]=[CH:28][C:27]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:32][C:31]=1[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:20])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[CH:5]=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 665874424-(Piperidin-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamineHCID 86705961N-(2-chloropyridin-4-yl)-3-(trifluoromethyl)benzamide

生成物 1

HCID 66586960N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-chloropyridin-4-yl)-3-(trifluoromethyl)benzamide (350 mg, 1.16 mmol, 1.00 equiv), 4-(piperidin-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine (430 mg, 1.42 mmol, 1.20 equiv), Pd(PPh3)2Cl2 (81.7 mg, 0.12 mmol, 0.10 equiv), K3PO4.7H2O (790 mg, 2.33 mmol, 2.00 equiv), X—PHOS (91.6 mg, 0.23 mmol, 0.20 equiv) in DME/H2O (10:1) (30/3 mL). The resulting solution was stirred for 2 h at 80° C. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The residual solution was diluted with 50 mL of water. The resulting solution was extracted with 2×50 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (100˜100:1˜40:1). This resulted in 350 mg (67%) of N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide as a yellow solid

後処理

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe residual solution was diluted with 50 mL of water
  5. extractionThe resulting solution was extracted with 2×50 mL of dichloromethane
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThis resulted in 350 mg (67%) of N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide as a yellow solid

出典と根拠

ORDレコード
ord-1bdf87d6b3354195b22b98dc1ca56370
出典データセット
uspto-grants-2014_12
特許番号
US08916569B2

反応ノート

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