1-Hydroxybenzotriazole → 7-(4-methylphenyl)-N-[1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]piperidin-4-yl]-2,3-dihydro-1-benzooxepine-4-carboxamide

HRID 1169408ノート

反応式

HRID 1169408 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[NH2:46][CH:47]1[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][N:55]([CH3:62])[CH:56]2[CH2:61][CH2:60][O:59][CH2:58][CH2:57]2)[CH2:49][CH2:48]1>C(#N)C.C(N(CC)CC)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18]([NH:46][CH:47]4[CH2:48][CH2:49][N:50]([CH2:53][CH2:54][N:55]([CH3:62])[CH:56]5[CH2:61][CH2:60][O:59][CH2:58][CH2:57]5)[CH2:51][CH2:52]4)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acidHCID 229899814-amino-1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]piperidine dihydrochloride

生成物 1

HCID 229901477-(4-methylphenyl)-N-[1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]piperidin-4-yl]-2,3-dihydro-1-benzooxepine-4-carboxamide収率 36.7%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 8471Triethylamine溶媒

実験手順

Into a solution of 7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxylic acid (150 mg) and 1-hydroxybenzotriazole (0.14 g) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.20 g), and the resulting mixture was stirred for one hour. Into the reaction mixture was added a solution of 4-amino-1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]piperidine dihydrochloride (282 mg), triethylamine (0.15 ml.) and diazabicyclo[5,4,0]-7-undecene (0.37 g) in acetonitrile (15 ml), and the resulting mixture was stirred for 18 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. The resulting organic layer was evaporated to remove the solvent, and then the residue was subjected to purification using column chromatography (triethylamine/ethanol/ethyl acetate 1:10:10) and further to recrystallization (ethyl acetate/hexane) to obtain 7-(4-methylphenyl)-N-[1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]piperidin-4-yl]-2,3-dihydro-1-benzooxepine-4-carboxamide (compound 62) (99 mg) as colorless crystals.

後処理

  1. stirringthe resulting mixture was stirred for 18 hours
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
  3. additionwas added to the residue
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  6. dry with materialwas dried with magnesium sulfate
  7. customThe resulting organic layer was evaporated
  8. customto remove the solvent
  9. customthe residue was subjected to purification
  10. customfurther to recrystallization (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-453d39eabfa84d4d969ec316f3bb04f6
出典データセット
uspto-grants-2003_09
特許番号
US06627651B1

反応ノート

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