Dimethylformamide → 3-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbonitrile

HRID 68968Notes

Reaction equation

HRID 68968 reaction equation
Cl[C:2]1[C:7]([CH2:8][N:9]([CH2:23][C:24]2[CH:41]=[CH:40][C:27]3[N:28]([CH2:38][CH3:39])[C:29](=[O:37])[C:30]([CH3:36])([CH3:35])[C:31](=[O:34])[N:32]([CH3:33])[C:26]=3[CH:25]=2)[CH2:10][CH2:11][N:12]2[CH:17]=[CH:16][C:15]3[O:18][C:19]([CH3:21])=[CH:20][C:14]=3[C:13]2=[O:22])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:42][N:43](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn].O>[CH2:38]([N:28]1[C:29](=[O:37])[C:30]([CH3:36])([CH3:35])[C:31](=[O:34])[N:32]([CH3:33])[C:26]2[CH:25]=[C:24]([CH2:23][N:9]([CH2:8][C:7]3[C:2]([C:42]#[N:43])=[N:3][CH:4]=[CH:5][CH:6]=3)[CH2:10][CH2:11][N:12]3[CH:17]=[CH:16][C:15]4[O:18][C:19]([CH3:21])=[CH:20][C:14]=4[C:13]3=[O:22])[CH:41]=[CH:40][C:27]1=2)[CH3:39]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 866704802-Chloro-3-({(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(2-methyl-4-oxo-4-H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine

Product 1

HCID 706571733-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbonitrile

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

2-Chloro-3-({(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(2-methyl-4-oxo-4-H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine (0.3 g), zinc cyanide (120 mg), tris(dibenzylideneacetone)dipalladium (24 mg), 1,1′-bis(diphenylphosphino)ferrocene (14 mg), and zinc powder (3.4 mg) were added to DMF (3 ml), and the mixture was heated at 95° C. for 3 hours. The reaction liquid was cooled to room temperature. Water was added to the reaction mixture and subjected to celite filtration. Extraction with ethyl acetate was performed. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=93:7). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether to give the title compound (1.35 g) as a white powder.

Workup

  1. customThe reaction liquid
  2. temperaturewas cooled to room temperature
  3. filtrationsubjected to celite filtration
  4. extractionExtraction with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=93:7)
  8. customcondensed under reduced pressure
  9. customthe residue was recrystallized from ether

Sources & evidence

ORD record
ord-4dd881faa6a244ee90c0860607a2b6f7
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Reaction notes

Loading…