Acetate → HCID 178491350, compound

HRID 929677Notes

Reaction equation

HRID 929677 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([NH:11][CH2:12][C:13]2[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:14]=2[O:21][CH3:22])=[NH:10])[CH:5]=[CH:4][CH:3]=1.[Br-].[CH2:24]([Zn+])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])(=O)C>[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH2:24]([C:2]1[N:7]=[C:6]([NH:8][C:9]([NH:11][CH2:12][C:13]2[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:14]=2[O:21][CH3:22])=[NH:10])[CH:5]=[CH:4][CH:3]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 175AcetateHCID 178419772HCID 178419772, compound2×HCID 178491347HCID 178491347, compound

Product 1

HCID 178491350HCID 178491350, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 178418807HCID 178418807, compoundCatalyst

Procedure

The preparation was carried out analogously to Example 67, using 0.200 g (0.548 mmol) N-(6-bromopyridin-2-yl)-N′-(2,6-dimethoxybenzyl)guanidine and 2.74 mL (1.369 mmol) of the benzyl zinc bromide solution (0.5 M in tetrahydrofuran) under Pd catalysis with 20 mg (0.055 mmol) [1,1′-bis-(diphenylphosphino)ferrocene]palladium(II) chloride-methylene chloride. The mixture was likewise heated under reflux under a nitrogen atmosphere, first for 4 hr, and then after repeated additions of 2.43 mL (1.213 mmol) of the 0.5 M benzyl zinc bromide solution and 20 mg (0.055 mmol) Pd catalyst for an additional 8 hr, i.e., for a total of 12 hr of heating. After appropriate workup and purification via preparative HPLC (Merck Chromolith RP-18 100×25 mm, eluent: water/acetonitrile/0.1 M acetic acid), 95 mg (0.216 mmol, 40%) pure N-(6-benzylpyridin-2-yl)-N′-(2,6-dimethoxybenzyl)guanidine was obtained in the form of the acetate salt (base/acetate in a ratio of 1:1).

Workup

  1. temperatureThe mixture was likewise heated
  2. temperatureunder reflux under a nitrogen atmosphere, first for 4 hr
  3. customfor an additional 8 hr
  4. temperaturei.e., for a total of 12 hr of heating
  5. customAfter appropriate workup and purification via preparative HPLC (Merck Chromolith RP-18 100×25 mm, eluent: water/acetonitrile/0.1 M acetic acid)

Sources & evidence

ORD record
ord-baa4b28146144703b36c4d0d70ecbdad
Source dataset
uspto-grants-2016_03
Patent number
US09296697B2

Reaction notes

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