1-Hydroxybenzotriazole → N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxamide

HRID 2228244Notes

Reaction equation

HRID 2228244 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][CH2:21][CH2:20][C:19]([C:23](O)=[O:24])=[CH:18][C:17]=4[CH:26]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:49][N:50]([CH2:57][C:58]1[CH:64]=[CH:63][C:61]([NH2:62])=[CH:60][CH:59]=1)[CH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>CN(C=O)C.C(N(CC)CC)C>[CH3:49][N:50]([CH2:57][C:58]1[CH:59]=[CH:60][C:61]([NH:62][C:23]([C:19]2[CH2:20][CH2:21][S:22][C:16]3[CH:15]=[CH:14][C:13]([C:10]4[CH:11]=[CH:12][C:7]([N:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)=[CH:8][CH:9]=4)=[CH:26][C:17]=3[CH:18]=2)=[O:24])=[CH:63][CH:64]=1)[CH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 184722757-(4-Morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 18472652N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxamideYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxylic acid (150 mg) and 1-hydroxybenzotriazole (0.11 g) in DMF (5 ml) was added at room temperature 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.16 g), and the mixture was stirred for 1 hour. To the mixture was added a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline (135 mg) and triethylamine (0.11 ml) in DMF (5 ml), and the mixture was stirred for 18 hours. Under reduced pressure, the mixture was concentrated, and to the mixture was added water. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with column chromatography (ethanol/ethyl acetate=1:2) to give yellow crystals of N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 285) (113.9 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. concentrationUnder reduced pressure, the mixture was concentrated
  3. additionto the mixture was added water
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried with magnesium sulfate
  7. customUnder reduced pressure, the solvent was evaporated
  8. customthe residue was purified with column chromatography (ethanol/ethyl acetate=1:2)

Sources & evidence

ORD record
ord-f11bfac089fa4322af301b74f3fbecd4
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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