Acetate → HCID 178489505, compound

HRID 929676Notes

Reaction equation

HRID 929676 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=[NH:10])[CH:5]=[CH:4][CH:3]=1.[Br-].[CH2:22]([Zn+])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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.O.C(#N)C>[CH2:22]([C:2]1[N:7]=[C:6]([NH:8][C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=[NH:10])[CH:5]=[CH:4][CH:3]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 3

HCID 175AcetateHCID 178419772HCID 178419772, compound2×HCID 178489504HCID 178489504, compound

Product 1

HCID 178489505HCID 178489505, compoundYield 7.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

The preparation was carried out analogously to Example 67, using 0.200 g (0.597 mmol) N-(6-bromopyridin-2-yl)-N′-(2-methoxybenzyl)guanidine and 2.98 mL (1.491 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 a nitrogen atmosphere, first under reflux for 9 hr, and then after repeated additions of 2.98 mL (1.491 mmol) of the 0.5 M benzyl zinc bromide solution and 20 mg (0.055 mmol) Pd catalyst the mixture was heated for an additional 8 hr and stirred for an additional 8 hr. After appropriate workup and purification via two preparative HPLC procedures (1× via Waters, XTerra RP-18 and Merck, 1× Chromolith RP-18 100×25 mm, each eluent: water/acetonitrile/0.1 M acetic acid), 18 mg (0.044 mmol, 7%) N-(6-benzylpyridin-2-yl)-N′-(2-methoxybenzyl)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 under a nitrogen atmosphere
  2. temperaturefirst under reflux for 9 hr
  3. temperaturewas heated for an additional 8 hr
  4. customAfter appropriate workup and purification via two preparative HPLC procedures (1× via Waters, XTerra

Sources & evidence

ORD record
ord-b02dcd39ff5344ff9af89d60a86880ed
Source dataset
uspto-grants-2016_03
Patent number
US09296697B2

Reaction notes

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