Hydrochloric Acid → N-methyl-N'-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-pyrimidine-4,6-diamine

HRID 409659Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH3:9])[CH:3]=1.[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=2)[CH2:13][CH2:12]1.Cl>O1CCOCC1>[CH3:9][NH:8][C:4]1[CH:3]=[C:2]([NH:24][C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([CH2:17][N:14]3[CH2:13][CH2:12][N:11]([CH3:10])[CH2:16][CH2:15]3)[CH:19]=2)[N:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of (6-chloro-pyrimidin-4-yl)-methyl-amine (385 mg, 2.68 mmol, 1.1 equiv), 3-(4-methyl-piperazin-1-ylmethyl)-phenylamine (500 mg, 2.44 mmol) and 4N HCl in dioxane (7 mL) is heated in a sealed tube to 150° C. for 17.5 h. The solvent is removed and the residue diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted with DCM and DCM/MeOH (95:5). The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the residue by silica gel MPLC (DCM/MeOH+1% NH3aq, 95:5) affords the title compound as a beige solid: ESI-MS: 313.2 [MH]+; tR=1.00 min (purity: 100%, system 1); TLC: Rf=0.05 (DCM/MeOH+1% NH3aq, 9:1).

Workup

customThe solvent is removed
additionthe residue diluted with DCM
customThe aqueous layer is separated
extractionextracted with DCM and DCM/MeOH (95:5)
washThe organic phase is washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customPurification of the residue by silica gel MPLC (DCM/MeOH+1% NH3aq, 95:5)

Sources & evidence

ORD record: ord-1c9a26ae5e3747fe8fc28b642bafd10c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759517B2

Reaction notes

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