1-Hydroxybenzotriazole → 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl-7,8-dihydro-6H-cyclohepta[b]thiophene-5-carboxamide

HRID 1169419ノート

反応式

HRID 1169419 の反応式
CC1C=CC([C:8]2[S:12][C:11]3[CH2:13][CH2:14][CH2:15][C:16]([C:18]([OH:20])=O)=[CH:17][C:10]=3[CH:9]=2)=CC=1.O[N:22]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[CH3:45][N:46]([CH2:53][C@H:54]1[CH2:59][CH2:58][C@H:57](N)[CH2:56][CH2:55]1)[CH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.C1CCN2C(=NCCC2)CC1>C(#N)C.C(N(CC)CC)C>[CH3:45][N:46]([CH2:53][CH:54]1[CH2:59][CH2:58][CH:57]([C:8]2[S:12][C:11]3[CH2:13][CH2:14][CH2:15][C:16]([C:18]([NH2:22])=[O:20])=[CH:17][C:10]=3[CH:9]=2)[CH2:56][CH2:55]1)[CH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 229900592-(4-methylphenyl)-7,8-dihydro-6H-cyclohepta[b]thiophene-5-carboxylic acidHCID 178484107HCID 178484107、化合物

生成物 1

HCID 867591864-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl-7,8-dihydro-6H-cyclohepta[b]thiophene-5-carboxamide収率 64.5%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 8471Triethylamine溶媒

実験手順

Into a suspension of 2-(4-methylphenyl)-7,8-dihydro-6H-cyclohepta[b]thiophene-5-carboxylic acid (150 mg) and 1-hydroxybenzotriazole (107 mg) in acetonitrile (15 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (152 mg), and the resulting mixture was stirred for 2 hours. Into the reaction mixture was added a solution of trans-4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexylamine dihydrochloride (236 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (240 mg) and triethylamine (0.15 ml) in acetonitrile (20 ml), and the resulting mixture was stirred for 20 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. After the resulting organic layer was concentrated under reduced pressure to remove the solvent, the residue was subjected to purification using column chromatography (ethanol/ethyl acetate 1:2→2:3) and to recrystallization (ethyl acetate/hexane) to obtain trans-2-(4-methylphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl-7,8-dihydro-6H-cyclohepta[b]thiophene-5-carboxamide (compound 69) (137 mg) as light yellow crystals.

後処理

  1. stirringthe resulting mixture was stirred for 20 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. concentrationAfter the resulting organic layer was concentrated under reduced pressure
  8. customto remove the solvent
  9. customthe residue was subjected to purification
  10. customto recrystallization (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-2e1021b44495454e82aee970c1f43dbb
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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