Chloroacetic anhydride → (S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 1378201노트

반응식

HRID 1378201 반응식
[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[N:18][OH:19])[NH2:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:24][CH2:25][C:26](OC(=O)CCl)=O>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[N:17]=[C:26]([CH2:25][Cl:24])[O:19][N:18]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 10946Chloroacetic anhydrideHCID 53703069(S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime

생성물 1

HCID 54468676(S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one수율 75.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A suspension of 7.07 g (21.3 mmol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime in 50 ml of N,N-dimethylformamide was treated with 4.0 g (23.4 mmol) of chloroacetic anhydride. The yellow solution obtained was stirred at 105° for 2 hrs. and then completely freed from the solvents. The oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent and the oily product obtained was recrystallized from ethyl acetate/ether. The mother liquor was concentrated, the residue was again chromatographed over silica gel with acetonitrile as the eluent and the additional portion of product obtained was recrystallized from ethyl acetate/ether. There were obtained a total of 6.27 g (75%) of (S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one as white crystals; m.p. 184°-186° and [α]D20 =+36.1° (MeOH, c=1%).

후처리

  1. customThe yellow solution obtained
  2. customThe oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent
  3. customthe oily product obtained
  4. customwas recrystallized from ethyl acetate/ether
  5. concentrationThe mother liquor was concentrated
  6. customthe residue was again chromatographed over silica gel with acetonitrile as the eluent
  7. customthe additional portion of product obtained
  8. customwas recrystallized from ethyl acetate/ether

출처 및 근거

ORD 기록
ord-f07d637f349747d09dc0314f5a50fe28
출처 데이터셋
uspto-grants-1997_09
특허 번호
US05665718

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