1-Methylpiperazine → HCID 49838144, compound

HRID 472284Notes

Reaction equation

HRID 472284 reaction equation
Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:9]2[N:10]=[C:3]3[C:2]([N:24]4[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]4)=[CH:7][CH:6]=[CH:5][N:4]3[N:8]=2)=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67478829(8-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-(4-methoxy-phenyl)-amine

Product 1

HCID 49838144HCID 49838144, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To an oven dried tube was added (8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-(4-methoxy-phenyl)-amine (50.0 mg, 0.157 mmol), 1-methyl-piperazine (21.0 L, 0.189), palladium acetate (7.0 mg, 0.031 mmol), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (15.0 mg, 0.0315 mmol, X-Phos), potassium phosphate (83.0 mg, 0.391 mmol) and 1,4-dioxane (3 mL) and kept under an atmosphere of nitrogen. The tube was evacuated and backflushed with nitrogen three times. The tube was sealed and heated at 100° C. for 18 hours. The mixture was cooled to room temperature and diluted with dichloromethane (10 mL). The suspension was filtered and the filtrate was evaporated. The residue was purified via chromatography using amine modified silica gel column (4.7 g) and 5%→100% ethyl acetate:hexane solvent gradient. The title compound was isolated as a tan foam (0.025 g, 47%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.04 (dd, J=6.5, 1.0 Hz, 1H), 7.51-7.46 (m, 2H), 6.93-6.88 (m, 2H), 6.74 (dd, J=7.8, 1.0 Hz, 1H), 6.58 (s, 1H), 3.80 (s, 3H), 3.55-3.45 (m, 4H), 2.71-2.65 (m, 4H), 2.39 (s, 3H). MS=339 (MH)+.

Workup

  1. customTo an oven dried tube
  2. customThe tube was evacuated
  3. customThe tube was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with dichloromethane (10 mL)
  6. filtrationThe suspension was filtered
  7. customthe filtrate was evaporated
  8. customThe residue was purified via chromatography

Sources & evidence

ORD record
ord-7450850b20bc483ca41c3e83b1592397
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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