1-Hydroxybenzotriazole → N-[4-[N-(2-ethoxycarbonylethyl)-N-methylaminomethyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide

HRID 1978560Notes

Reaction equation

HRID 1978560 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16]4[S:22](=[O:24])(=[O:23])[CH2:21][CH2:20][C:19]([C:25](O)=[O:26])=[CH:18][C:17]=4[CH:28]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[NH2:51][C:52]1[CH:67]=[CH:66][C:55]([CH2:56][N:57]([CH2:59][CH2:60][C:61]([O:63][CH2:64][CH3:65])=[O:62])[CH3:58])=[CH:54][CH:53]=1>CN(C=O)C.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[CH2:64]([O:63][C:61]([CH2:60][CH2:59][N:57]([CH2:56][C:55]1[CH:66]=[CH:67][C:52]([NH:51][C:25]([C:19]2[CH2:20][CH2:21][S:22](=[O:24])(=[O:23])[C:16]3[CH:17]=[CH:28][C:13]([C:10]4[CH:9]=[CH:8][C:7]([N:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)=[CH:12][CH:11]=4)=[CH:14][C:15]=3[CH:18]=2)=[O:26])=[CH:53][CH:54]=1)[CH3:58])=[O:62])[CH3:65]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 112349537-(4-Morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acidHCID 21995934ethyl 3-[N-(4-aminobenzyl)-N-methylamino]propionate

Product 1

HCID 21995877N-[4-[N-(2-ethoxycarbonylethyl)-N-methylaminomethyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideYield 57.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (150 mg) and 1-hydroxybenzotriazole (101 mg) in DMF (5 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (144 mg), and the mixture was stirred for 2 hours. To the mixture were added a solution of ethyl 3-[N-(4-aminobenzyl)-N-methylamino]propionate (133 mg) and triethylamine (0.1 ml) in DMF (5 ml) and a piece of 4-dimethylaminopyridine, and the mixture was stirred for 20 hours and concentrated under reduced pressure. To the residue was added water, and the mixture was extracted with dichloromethane. The organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with column chromatography (ethanol/ethyl acetate=1:9) and recrystallized from ethyl acetate/hexane to give yellow crystals of N-[4-[N-(2-ethoxycarbonylethyl)-N-methylaminomethyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 24) (133.6 mg).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionTo the residue was added water
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified with column chromatography (ethanol/ethyl acetate=1:9)
  8. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-9e477bea8d474de98a8044fba3b1e51f
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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