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

HRID 625400Notes

Reaction equation

HRID 625400 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-ab28d4eb9dcb4f0fa0486fb49ce18be4
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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