Tetrahydrofuran → HCID 178476647, compound

HRID 929674Notes

Reaction equation

HRID 929674 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([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])=[N:6][CH:7]=1.[Br-].[CH2:22]([Zn+])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[O:30]1CCCC1>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>[C:14]([OH:19])(=[O:30])[CH3:15].[CH2:22]([C:2]1[CH:3]=[CH:4][C:5]([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])=[N:6][CH:7]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 178419772HCID 178419772, compoundHCID 178489507HCID 178489507, compound

Product 1

HCID 178476647HCID 178476647, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Procedure

20 mg (0.055 mmol) [1,1′-bis-(diphenylphosphino)-ferrocene]palladium(II) chloride-methylene chloride was placed in 10 mL tetrahydrofuran, and the solution was deoxygenated with nitrogen. 0.200 g (0.523 mmol) N-(5-iodopyridin-2-yl)-N′-(2-methoxybenzyl)guanidine dissolved in 5 mL tetrahydrofuran was added dropwise through a septum (syringe technique), and the mixture was stirred for an additional 10 min. 4.19 mL (2.093 mmol) of a benzyl zinc bromide solution (0.5 M in tetrahydrofuran) was added dropwise under a nitrogen atmosphere. The reaction mixture was then heated under reflux for 4 hr. Since very little of the desired product was obtained, an additional 2.6 mL (1.308 mmol) of the benzyl zinc bromide solution was added. After additional heating under reflux for 4 hr the reaction went to completion. The reaction mixture was taken up in dichloromethane, and was extracted with saturated ammonium chloride solution (3×20 mL) and then with saturated sodium chloride solution (2×20 mL). The organic phase was dried over sodium sulfate and filtered, and the solvent was removed under vacuum. The residue was dissolved in acetonitrile/water (1:1) and 0.5 mL acetic acid, and purified via preparative HPLC (Waters, XTerra RP-18, eluent: water/acetonitrile/0.1 M acetic acid, with a flow rate of 30 mL/min and with gradients of 10% to 30% of the acetonitrile fraction in 20 min). The fractions containing pure product were combined and lyophilized with freeze drying, resulting in 0.072 g (1.771 mmol, 34%) N-(5-benzylpyridin-2-yl)-N′-(2-methoxybenzyl)guanidine in the form of the acetate salt (base/acetate in a ratio of 1:1).

Workup

  1. customthe solution was deoxygenated with nitrogen
  2. additionwas added dropwise through a septum (syringe technique)
  3. temperatureThe reaction mixture was then heated
  4. temperatureunder reflux for 4 hr

Sources & evidence

ORD record
ord-c30b786ce0734cd9a726620f7ad7d99e
Source dataset
uspto-grants-2016_03
Patent number
US09296697B2

Reaction notes

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