Methanol → 5,11-Dihydro-11-[(4-methoxyphenyl)methyl]-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

HRID 2380220Notes

Reaction equation

HRID 2380220 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9]([C:11]2[C:12]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:10])=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].CO.O1CCCC1>O1CCOCC1.C(O)(=O)C>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:17]2[C:12]3[N:13]=[CH:14][CH:15]=[CH:16][C:11]=3[C:9](=[O:10])[NH:8][C:7]3[CH:6]=[CH:5][CH:4]=[N:3][C:2]2=3)=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 24758Sodium hydride2×HCID 3320057N-(2-chloropyridin-3-yl)-2-[(4-methoxyphenyl)methylamino]pyridine-3-carboxamide

Product 1

HCID 148738035,11-Dihydro-11-[(4-methoxyphenyl)methyl]-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

16.7 g (0.0453 mol) of the product obtained in step b) were dissolved in 150 ml of absolute dioxane, and the resulting solution was admixed with 6.7 g (0.14 mol) of a 50% dispersion of sodium hydride in mineral oil. Thereafter, the mixture--while protected against the external atmosphere by a low flow of nitrogen--was refluxed until no starting material could be detected by TLC. The surplus of sodium hydride was decomposed by cautious addition of 10 ml of a mixture of methanol and tetrahydrofuran (50/50 v/v). The reaction mixture was neutralized by addition of acetic acid and then was evaporated in vacuo. The residue was purified by column chromatography on silica gel (0.2-0.5 mm) using successively dichloromethane/ethyl acetate 10/1 (v/v) and dichloromethane/ethyl acetate 1/1 (v/v) as eluents. The crystalline product obtained by evaporation of suitable fractions was recrystallized from acetonitrile and 2-propanol. The product had a m.p. of 213°-215° C. and was identified as 5,11-dihydro- 11-[(4-methoxyphenyl)-methyl]-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one. The yield was 10.3 g (68% of theory).

Workup

  1. temperaturewas refluxed until no starting material
  2. customwas evaporated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (0.2-0.5 mm)
  4. customThe crystalline product obtained by evaporation of suitable fractions
  5. customwas recrystallized from acetonitrile and 2-propanol

Sources & evidence

ORD record
ord-2c23d15104ea42bc852704a0525f99ad
Source dataset
uspto-grants-1994_11
Patent number
US05366972

Reaction notes

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