Pyrrolidine → (S)-8-chloro-1-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo-[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 1737366노트

반응식

HRID 1737366 반응식
[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21]Cl)[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>O1CCCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21][N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 31268PyrrolidineHCID 70067673(S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

생성물 1

HCID 70068062(S)-8-chloro-1-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo-[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one수율 44%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 1.3 g (0.0032mol) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in 15 ml of tetrahydrofuran was treated with 4 ml (0.048 mol) of pyrrolidine and stirred at 50° for 96 hrs. All volatiles were removed in a water-jet vacuum and the residue was taken up with ethyl acetate and water. The organic phase was dried over magnesium sulphate, concentrated and the residue remaining was chromatographed over silica gel with methylene chloride/methanol 95:5 as the eluent. After recrystallization from ethyl acetate there was obtained 0.62 g (44%) of (S)-8-chloro-1-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in the form of white crystals; m.p. 213-214° and [α]D20 =-71.2° (MeOH, c=1%).

후처리

  1. customAll volatiles were removed in a water-jet vacuum
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. concentrationconcentrated
  4. customthe residue remaining was chromatographed over silica gel with methylene chloride/methanol 95:5 as the eluent
  5. customAfter recrystallization from ethyl acetate

출처 및 근거

ORD 기록
ord-6149be903ab743caa3c6dcafce98e107
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05962450

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