Hydrazine hydrate (1:1) → 2-(aminomethyl)-1-(benzhydryloxy)-5-((4-methoxybenzyl)oxy)pyridin-4(1H)-one

HRID 627293Notes

Reaction equation

HRID 627293 reaction equation
[CH:1]([O:14][N:15]1[CH:20]=[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18](=[O:31])[CH:17]=[C:16]1[CH2:32][N:33]1C(=O)C2C(=CC=CC=2)C1=O)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>C(Cl)(Cl)Cl.CO>[NH2:33][CH2:32][C:16]1[N:15]([O:14][CH:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:20]=[C:19]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[C:18](=[O:31])[CH:17]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)3×HCID 150932422-((1-(Benzhydryloxy)-5-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)isoindoline-1,3-dione2×

Product 1

HCID 150932432-(aminomethyl)-1-(benzhydryloxy)-5-((4-methoxybenzyl)oxy)pyridin-4(1H)-oneYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 2-((1-(benzhydryloxy)-5-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)isoindoline-1,3-dione (Intermediate 292, 1.66 g, 2.90 mmol) in chloroform (20 mL) and methanol (10 mL) at room temperature was added hydrazine monohydrate (0.284 mL, 5.80 mmol). The reaction mixture was stirred overnight at room temperature. Another 1 eq of hydrazine monohydrate was added. After 3 hours still see starting material. Added another 1 eq of hydrazine monohydrate. After 2 hours the reaction mixture was filtered to remove solids. The filtrate was concentrated. The residue was triturated with MeOH and ether and the solids filtered off. This was repeated twice more. The resulting solid was triturated once with chloroform and MeOH and the solids removed by filtration. The filtrate was concentrated to afford a yellow foam (1.01 g, 79%).

Workup

  1. waitAfter 3 hours still see starting
  2. filtrationAfter 2 hours the reaction mixture was filtered
  3. customto remove solids
  4. concentrationThe filtrate was concentrated
  5. customThe residue was triturated with MeOH and ether
  6. filtrationthe solids filtered off
  7. customThe resulting solid was triturated once with chloroform and MeOH
  8. customthe solids removed by filtration
  9. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-8a25a89803e34d5997e1ab5e6575e89b
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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