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

반응식

HRID 1184654 반응식
[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

참가 물질

5

반응물 2

HCID 160352-Chloroethyl isocyanateHCID 216237Tolvaptan

생성물 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)carbamate수율 82%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9557162d57b747b49db1b568ee972bde
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669229B2

연결된 노트

불러오는 중…