Triphenylarsine → 4-Chloro-6-(2-nitro-5-(piperidin-1-yl)phenyl)pyrimidine

HRID 625219Notes

Reaction equation

HRID 625219 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1)([O-:3])=[O:2].[Cl:25][C:26]1[CH:31]=[C:30](Cl)[N:29]=[CH:28][N:27]=1.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[Cl:25][C:26]1[CH:31]=[C:30]([C:5]2[CH:6]=[C:7]([N:10]3[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]3)[CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])[N:29]=[CH:28][N:27]=1

Participants

8

Reactant 4

HCID 11773TriphenylarsineHCID 62657Potassium Phosphate, TribasicHCID 709434,6-DichloropyrimidineHCID 66587487HCID 66587487, compound

Product 1

HCID 867059284-Chloro-6-(2-nitro-5-(piperidin-1-yl)phenyl)pyrimidine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-(4-nitro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (5 g, 15.06 mmol, 1.00 equiv) in 1,4-dioxane (150 mL), water (25 mL), 4,6-dichloropyrimidine (5.54 g, 37.69 mmol, 2.50 equiv), Pd(PPh3)2Cl2 (500 mg, 0.75 mmol, 0.05 equiv), triphenylarsine (460 mg, 1.50 mmol, 0.10 equiv), and K3PO4 (4.79 g, 22.59 mmol, 1.50 equiv). The resulting solution was stirred overnight at 75° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:10). This resulted in 2.5 g (47%) of 4-chloro-6-(2-nitro-5-(piperidin-1-yl)phenyl)pyrimidine as a yellow solid.

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. washeluted with ethyl acetate/petroleum ether (1:10)
  5. customThis resulted in 2.5 g (47%) of 4-chloro-6-(2-nitro-5-(piperidin-1-yl)phenyl)pyrimidine as a yellow solid

Sources & evidence

ORD record
ord-5bfa7597ef794181a5ebe8847b9796e1
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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