1-Benzylpiperidin-3-amine → HCID 59304415, compound

HRID 2239828Notes

Reaction equation

HRID 2239828 reaction equation
OC(C(F)(F)F)=O.C([N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([NH:21][C:22]2[CH:23]=[C:24]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH2:39][CH3:40])=[CH:34][CH:33]=3)[C:25]3[N:26]([CH:28]=[CH:29][N:30]=3)[N:27]=2)[CH2:16]1)C1C=CC=CC=1.C(N1CCCC(N)C1)C1C=CC=CC=1>C(O)(=O)C.[Pd].CO>[CH2:39]([O:38][C:35]1[CH:34]=[CH:33][C:32]([NH:31][C:24]2[C:25]3[N:26]([CH:28]=[CH:29][N:30]=3)[N:27]=[C:22]([NH:21][CH:17]3[CH2:18][CH2:19][CH2:20][NH:15][CH2:16]3)[CH:23]=2)=[CH:37][CH:36]=1)[CH3:40]

Participants

6

Reactant 2

HCID 4216941-Benzylpiperidin-3-amineHCID 86611718HCID 86611718, compound

Product 1

HCID 59304415HCID 59304415, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a mixture of a N-(1-benzylpiperidin-3-yl)-N8-(4-ethoxyphenyl)imidazo[1,2-b]pyridazine-6,8-diamine TFA salt (14 mg, 0.021 mmol), prepared by the method of example I(1) using 1-benzylpiperidin-3-amine in place of trans-1,4-diaminocyclohexane in step (1d), and MeOH (5 mL) in a 500 ml PARR bottle was added 10% Pd/C (20 mg) and 3 drops of glacial acetic acid. The PARR bottle was then charged with H2 at 55 psi and allow to shake at room temperature for hours. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was purified by preparative HPLC followed by neutralization with ion exchange resin to furnish 0.5 mg (7%) of the title compound 1H NMR (500 MHz, MeOH) δ ppm 7.57 (1H, s), 7.31 (1H, s), 7.24 (2H, d, J=8.7 Hz), 6.97 (2H, d, J=8.7 Hz), 5.89 (1H, s), 4.05 (2H, q, J=6.9 Hz), 3.85 (1H, m), 3.45 (1H, m), 3.10 (1H, m), 2.85 (1H, m), 2.75 (1H, m), 2.05 (1H, m), 1.90 (1H, m), 1.70 (1H, m), 1.55 (1H, m), 1.39 (3H, t, J=6.9 Hz), LC/MS, m/e 353 (M+1). HPLC Rt, 2.04 min. YMC ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. additionThe PARR bottle was then charged with H2 at 55 psi
  2. waitto shake at room temperature for hours
  3. filtrationThe reaction mixture was then filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0bd2c2408eba4b05aac5c85a784a20f9
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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