2-Chloroethyl isocyanate → {7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl} (2-chloroethyl)carbamate

HRID 1184654

反応式

HRID 1184654 の反応式
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=3[CH:24]([OH:32])[CH2:23][CH2:22][CH2:21]2)=[O:19])=[C:15]([CH3:17])[CH:16]=1)=[O:9].[Cl:33][CH2:34][CH2:35][N:36]=[C:37]=[O:38]>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[Cl:31][C:29]1[CH:28]=[CH:27][C:26]2[N:20]([C:18](=[O:19])[C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:7]4[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=4[CH3:1])=[CH:16][C:15]=3[CH3:17])[CH2:21][CH2:22][CH2:23][CH:24]([O:32][C:37](=[O:38])[NH:36][CH2:35][CH2:34][Cl:33])[C:25]=2[CH:30]=1

参加物

5

反応物 2

HCID 160352-Chloroethyl isocyanateHCID 216237Tolvaptan

生成物 1

HCID 86708937{7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl} (2-chloroethyl)carbamate収率 82%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

Tolvaptan (1.0 g, 2.2 mmol) was suspended in toluene (7 ml). 2-Chloroethyl isocyanate (0.28 ml, 3.3 mmol) and 4-dimethylaminopyridine (DMAP) (27 mg, 0.22 mmol) were added thereto, and the mixture was stirred at 80° C. for 24 hours. After cooling to room temperature, the insoluble materials were filtered off and washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=54:46→33:67). The purified product was concentrated under reduced pressure to obtain 1.0 g of {7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl}(2-chloroethyl)carbamate as white amorphous solid.

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationthe insoluble materials were filtered off
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=54:46→33:67)
  6. concentrationThe purified product was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-9557162d57b747b49db1b568ee972bde
出典データセット
uspto-grants-2014_03
特許番号
US08669229B2

関連ノート

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