Water → bis(4-methylpiperazin-1-yl)methanone

HRID 2200886Notes

Reaction equation

HRID 2200886 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C[N:9]([C:11]([O:15]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:32][CH2:33][N:34]([CH:38](C)C)[CH:35](C)[CH3:36].O>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:11]([N:9]2[CH2:36][CH2:35][N:34]([CH3:38])[CH2:33][CH2:32]2)=[O:15])[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 962WaterHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 515613bis(4-methylpiperazin-1-yl)methanoneYield 19%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In THF (20 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amine)pyrimidine-5-carboxylic acid (153 mg, 0.41 mmol), 1-methylpiperazine (49 mg, 0.49 mmol) and HATU (188 mg, 0.49 mmol). The solution was cooled in an ice bath then DIEA was added dropwisely (0.14 mL, 0.82 mmol). The reaction was conducted at ambient temperature for 8 h, followed by addition of water (20 mL) and extraction with ethyl acetate or DCM. The organic phase was dried, concentrated and purified by silica gel column chromatography (DCM/methanol=25/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidin-5-yl)(4-methylpiperazin-1-yl)ketone (35 mg, 19% yield).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. customThe organic phase was dried
  3. concentrationconcentrated
  4. custompurified by silica gel column chromatography (DCM/methanol=25/1)

Sources & evidence

ORD record
ord-22093cadf69e4511962a08139cb6ef57
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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