Hydrochloric Acid → 1-Acetyl-4-[(2-amino-6-methylpyridin-4-yl)methyl]piperazin-4-ium chloride

HRID 1814018Notes

Reaction equation

HRID 1814018 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[N:14]=[C:13]([NH:18]C(=O)OC(C)(C)C)[CH:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[ClH:26]>C(Cl)Cl.O1CCOCC1>[Cl-:26].[C:1]([N:4]1[CH2:5][CH2:6][NH+:7]([CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[N:14]=[C:13]([NH2:18])[CH:12]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 22504317tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methylpyridin-2-ylcarbamate

Product 1

HCID 865882691-Acetyl-4-[(2-amino-6-methylpyridin-4-yl)methyl]piperazin-4-ium chloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methylpyridin-2-ylcarbamate (13-3) was dissolved in CH2Cl2 and the solution was cooled to 0° C. 4.0M HCl in dioxane was added and the solution allowed to warm to room temperature. The reaction was concentrated in vacuo to afford 1-acetyl-4-[(2-amino-6-methylpyridin-4-yl)methyl]piperazin-4-ium chloride. 1-Acetyl-4-[(2-amino-6-methylpyridin-4-yl)methyl]piperazin-4-ium chloride (0.095 g, 0.30 mmol) was dissolved in 2 mL THF. 2-Chloro-1,3-thiazole-5-carbonitrile (0.051 g, 0.36 mmol) and sodium hydride (60% dispersion in mineral oil) (0.028 g, 1.19 mmol) were added and the solution was heated to 75° C. After 4 hours more 2-chloro-1,3-thiazole-5-carbonitrile (0.051 g, 0.36 mmol) was added. After 5.5 hours the solution was allowed to cool to room temperature and concentrated in vacuo. Acetic acid (0.070 mL, 1.19 mmol) was added and was concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient, 5-100% CH3CN/H2O+0.1% TFA). The fractions containing the desired compound were concentrated to dryness to afford the TFA salt of 13-4. TFA salt: 1H NMR (CD3OD) δ 8.04 (s, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 4.13 (bs, 2H), 3.74 (bs, 2H), 3.06 (bs, 6H), 2.61 (s, 3H), 2.13 (s, 3H). [M+H]+=357.1494.

Workup

  1. temperatureto warm to room temperature
  2. concentrationThe reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-1de79a93b6a3465295a1789f1e7c8180
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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