1-Methylpiperazine → HCID 3252419, compound
Reaction equation
Cl[C:2]1[C:3]([Cl:9])=[N:4][C:5](Cl)=[N:6][CH:7]=1.[CH3:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>>[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:5]2[N:6]=[C:7]([N:14]3[CH2:15][CH2:16][N:11]([CH3:10])[CH2:12][CH2:13]3)[CH:2]=[C:3]([Cl:9])[N:4]=2)[CH2:13][CH2:12]1Participants
Procedure
Trichloropyrimidine is added in portions to an ice cooled solution of N-methylpiperazine (40 g) in alcohol (200 ml). The mixture is then heated at 60° for 2 hr. The mixture is concentrated and chromatographed on silica gel with 2 to 5% methanol in methylene chloride to give 2,4-bis-[4-methylpiperazino]-6-chloropyrimidine. This material is heated at 130° in water (30 ml) with piperazine (32 g) in a Parr bomb for 20 hr. The product is partitioned between methylene chloride and aqueous sodium carbonate. The phases are separated and the organic phase is dried over sodium sulfate and concentrated to give 2,4-bis[1(4-methylpiperazino)]-6-piperazinopyimidine. This triamine is stirred in acetonitrile (200 ml) with 21-bromo-17α-hydroxypregna-4,9(11)-diene-3,20-dione (7.18 g) and potassium carbonate (2 g) for 20 hr. The mixture is partitioned between methylene chloride and aqueous sodium bicarbonate. The phases are separated and the organic phase is concentrated and chromatographed on silica gel (methylene chloride to 5% methanol and 0.5% ammonium hydroxide/methylene chloride) to give the free base corresponding to the title compound. The free base is dissolved in ethyl acetate and treated with methane sulfonic acid (2.22 g). The product is triturated with ether to give the title compound, bubbled at 110° without obvious decomp.
Workup
- temperatureThe mixture is then heated at 60° for 2 hr
- concentrationThe mixture is concentrated
- customchromatographed on silica gel with 2 to 5% methanol in methylene chloride
Sources & evidence
- ORD record
- ord-a1dfee7722bd439cabffcd6cf8e93a38
- Source dataset
- uspto-grants-1994_06
- Patent number
- US05322943
Reaction notes
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