Benzoic Acid → HCID 44200205, compound

HRID 1183097Notes

Reaction equation

HRID 1183097 reaction equation
[ClH:1].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:23][N:24]1[C:30](=[O:31])[C:29]([CH3:33])([CH3:32])[C:28](=[O:34])[N:27]([CH3:35])[C:26]2[CH:36]=[C:37]([O:40][CH2:41][CH2:42][CH2:43][N:44]([CH2:52][CH2:53][NH:54][CH3:55])[CH2:45][C:46]3[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=3)[CH:38]=[CH:39][C:25]1=2.[C:56](O)(=[O:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>C(OCC)(=O)C.O.CN(C=O)C>[ClH:1].[ClH:1].[CH3:55][N:54]([CH2:53][CH2:52][N:44]([CH2:45][C:46]1[CH:47]=[CH:48][N:49]=[CH:50][CH:51]=1)[CH2:43][CH2:42][CH2:41][O:40][C:37]1[CH:38]=[CH:39][C:25]2[N:24]([CH3:23])[C:30](=[O:31])[C:29]([CH3:32])([CH3:33])[C:28](=[O:34])[N:27]([CH3:35])[C:26]=2[CH:36]=1)[C:56](=[O:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

8

Reactant 4

HCID 243Benzoic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68672813HCID 68672813, compound

Product 1

HCID 44200205HCID 44200205, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (WSC) (144 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (115 mg, 0.75 mmol) were added to a DMF solution (5 ml) of 1,3,3,5-tetramethyl-7-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (227 mg, 0.5 mmol) and benzoic acid (92 mg, 0.75 mmol), and stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with ethyl acetate was performed. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→10:1). The purified product was concentrated under reduced pressure, and a 4N-hydrogen chloride ethyl acetate solution (0.14 ml) was added to the residue (an ethyl acetate solution). The precipitated insoluble matter was collected by filtration, washed with ethyl acetate, and dried to thereby obtain 120.5 mg (yield: 40%) of N-methyl-N-(2-{pyridin-4-ylmethyl-[3-(1,3,3,5-tetramethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]amino}ethyl)benzamide dihydrochloride as a white powder.

Workup

  1. washThe organic layer was washed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→10:1)
  5. concentrationThe purified product was concentrated under reduced pressure
  6. additiona 4N-hydrogen chloride ethyl acetate solution (0.14 ml) was added to the residue (an ethyl acetate solution)
  7. filtrationThe precipitated insoluble matter was collected by filtration
  8. washwashed with ethyl acetate
  9. customdried

Sources & evidence

ORD record
ord-7563a181237f4985894303482c7a9f0c
Source dataset
uspto-grants-2014_03
Patent number
US08664217B2

Reaction notes

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