Isonicotinic Acid → N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)isonicotinamide

HRID 2196086Notes

Reaction equation

HRID 2196086 reaction equation
Cl.CN(C)CCCN=C=NCC.[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][NH:35][CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14].[C:44](O)(=[O:51])[C:45]1[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=1.ON1C2C=CC=CC=2N=N1>C(#N)C>[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][N:35]([CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[C:44](=[O:51])[C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14]

Participants

6

Reactant 4

HCID 5922Isonicotinic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 686730021-Ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino) propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 68675178N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)isonicotinamideYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (WSC) (0.16 g, 0.85 mmol) was added to an acetonitrile solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.3 g, 0.71 mmol), isonicotinic acid (96 mg, 0.78 mmol), and 1-hydroxybenzotriazole (HOBT) (0.138 g, 0.85 mmol), and then stirred at room temperature for 2 days. The solvent was concentrated under reduced pressure. Ethyl acetate and a sodium hydrogen carbonate aqueous solution were added to the reaction mixture, and stirred for 1 hour. Water was added to the reaction mixture, and extraction with ethyl acetate was conducted. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by medium pressure liquid chromatography (silica gel, dichloromethane:methanol=92:8). The purified product was concentrated under reduced pressure and crystallized from ethyl acetate, diethylether and n-hexane. The precipitated crystals were collected by filtration and dried to thereby obtain 0.21 g (yield:56%) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)isonicotinamide as a white powder.

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additionEthyl acetate and a sodium hydrogen carbonate aqueous solution were added to the reaction mixture
  3. stirringstirred for 1 hour
  4. additionWater was added to the reaction mixture, and extraction with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified by medium pressure liquid chromatography (silica gel, dichloromethane:methanol=92:8)
  9. concentrationThe purified product was concentrated under reduced pressure
  10. customcrystallized from ethyl acetate, diethylether and n-hexane
  11. filtrationThe precipitated crystals were collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-fbf7e66454f2447785eb5b73c8f4dc70
Source dataset
uspto-grants-2012_12
Patent number
US08338406B2

Reaction notes

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