Acetic Acid → HCID 59304460, compound

HRID 2239901Notes

Reaction equation

HRID 2239901 reaction equation
C([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:17]=[C:18]([N:25](CC3C=CC(OC)=CC=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:19]3[N:20]([CH:22]=[CH:23][N:24]=3)[N:21]=2)[CH2:11][CH2:10]1)C1C=CC=CC=1.CC(O)=O.[H][H].C(O)(C(F)(F)F)=O>[Pd].CO>[NH2:8][CH:9]1[CH2:10][CH2:11][N:12]([CH2:15][C:16]2[CH:17]=[C:18]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:19]3[N:20]([CH:22]=[CH:23][N:24]=3)[N:21]=2)[CH2:13][CH2:14]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 68482143HCID 68482143, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59304460HCID 59304460, compoundYield 49.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

In a Parr bottle was added 6-((4-(benzylamino)piperidin-1-yl)methyl)-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine (0.030 g, 0.056 mmol) from (1e), MeOH (7 ml), Pd/C (0.030 mg, 0.282 μmol) and AcOH (0.020 ml, 0.349 mmol). Added hydrogen to a pressure of 55 psi and let shake overnight. The suspension was filtered through celite and rinsed with MeOH, concentrated, and then diluted with TFA (1 ml). The mixture was allowed to stir at room temperature for 6 hours, concentrated and diluted with MeOH (2 ml) and purified by HPLC (10-75% MeOH/Water) to provide the title compound (0.009 g, 49.6% yield) as a TFA salt. 1H NMR (500 MHz, MeOH) δ ppm 8.08 (1H, d, J=2.75 Hz), 7.76 (1H, d, J=2.75 Hz), 7.47 (2H, dd, J=7.56, 3.44 Hz), 7.40-7.45 (2H, m), 7.25-7.31 (1H, m), 6.78 (1H, d, J=3.67 Hz), 4.40 (2H, d, J=3.21 Hz), 3.74 (2H, d, J=11.00 Hz), 3.46 (1H, d, J=3.67 Hz), 3.22 (2H, t, J=12.14 Hz), 2.25 (2H, d, J=14.20 Hz), 2.00 (2H, m). LC/MS, m/z 323 (M+1). HPLC Rt, 1.04 min. Waters Sunfire C18 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. filtrationThe suspension was filtered through celite
  2. washrinsed with MeOH
  3. concentrationconcentrated
  4. additiondiluted with TFA (1 ml)
  5. concentrationconcentrated
  6. additiondiluted with MeOH (2 ml)
  7. custompurified by HPLC (10-75% MeOH/Water)

Sources & evidence

ORD record
ord-de6ec30c06bf4b66b230e0b3ba0763d5
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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