1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-[(1RS,2SR)-1-[3-(1,1-difluoroethyl)benzyl]-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide

HRID 1610728ノート

反応式

HRID 1610728 の反応式
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[CH3:20])[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:23]1([C:34](O)=[O:35])[CH:24]=[CH:25][CH:26]=[C:27]2[CH2:33][CH2:32][CH2:31][CH:30]=[CH:29][C:28]=12.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(#N)C.C(OCC)(=O)C>[F:21][C:19]([C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[CH2:12][CH:2]([NH:1][C:34]([C:23]1[CH:24]=[CH:25][CH:26]=[C:27]2[CH2:33][CH2:32][CH2:31][CH:30]=[CH:29][C:28]=12)=[O:35])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4])([F:22])[CH3:20]

参加物

7

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22261599(1RS,2SR)-2-amino-3-[3-(1,1-difluoroethyl)phenyl]-1-(4-fluorophenyl)-1-propanolHCID 222620106,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid

生成物 1

HCID 22261915N-[(1RS,2SR)-1-[3-(1,1-difluoroethyl)benzyl]-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide収率 78%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (1RS,2SR)-2-amino-3-[3-(1,1-difluoroethyl)phenyl]-1-(4-fluorophenyl)-1-propanol (0.40 g, 1.42 mmol) in acetonitrile (10 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (0.28 g, 1.49 mmol) and 1-hydroxybenzotriazole monohydrate (0.22 g, 1.49 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.27 g, 1.49 mmol) was finally added. The mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1, 2:1) and recrystallization (hexane-ethyl acetate) to give N-[(1RS,2SR)-1-[3-(1,1-difluoroethyl)benzyl]-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide (0.50 g, 78%) as colorless crystals.

後処理

  1. additionwas finally added
  2. washwashed with saturated aqueous sodium hydrogen carbonate, water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1, 2:1) and recrystallization (hexane-ethyl acetate)

出典と根拠

ORDレコード
ord-70f82248b4f14b358fd3b50eb6a22c88
出典データセット
uspto-grants-2006_01
特許番号
US06982348B2

反応ノート

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