Borane → 7-(2-Chlorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine

HRID 80502

반응식

HRID 80502 반응식
O=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH2:13][CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16][CH:4]2[CH2:3]1.[H-].[Na+].Br[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[Cl:34].B>CN(C)C=O.CO>[Cl:34][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[CH2:27][N:8]1[C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH2:13][CH2:14][NH:15][CH2:16][CH:4]2[CH2:3][CH2:2]1

참가 물질

7

반응물 4

HCID 6331BoraneHCID 11905alpha-Bromo-o-chlorotolueneHCID 24758Sodium hydrideHCID 58284919tert-butyl 6-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,5]benzodiazepine-3(4H)-carboxylate

생성물 1

HCID 497642957-(2-Chlorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a solution of Example 1C (50 mg, 0.16 mmol) in N,N-dimethylformamide (1 mL) was added sodium hydride (65%, 6.98 mg, 0.19 mmol). The solution was allowed to stir at room temperature for 1 hour before addition of 1-(bromomethyl)-2-chlorobenzene (37.2 mg, 0.181 mmol). The reaction mixture was stirred overnight. The solution was concentrated. To the concentrate was added tetrahydrofuran (10 mL) followed by borane (1M in tetrahydrofuran, 1 mL, 1 mmol). The solution was heated in an 80° C. oil bath for 4 hours. Methanol (20 mL) was added and heating of the resultant solution was continued in the 80° C. bath for 1 hour before concentration. To the concentrate was added dichloromethane (10 mL), methanol (1 mL) and HCl (4M in dioxane, 2 mL) Once LC/MS analysis indicated the reaction was complete the solution was concentrated and purified by preparative HPLC to afford the title compound. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 7.46 (d, J=8.85 Hz, 1H) 7.28-7.38 (m, 3H) 6.95 (dd, J=7.93, 1.53 Hz, 1H) 6.87-6.92 (m, 1H) 6.82-6.87 (m, 1H) 6.70 (dd, J=7.78, 1.37 Hz, 1H) 4.56 (d, J=16.17 Hz, 1H) 4.36 (d, J=16.48 Hz, 1H) 3.46-3.56 (m, 1H) 3.35-3.43 (m, 2H) 3.06-3.28 (m, 4H) 2.93-3.02 (m, 2H) 1.89-1.99 (m, 1H) 1.70-1.79 (m, 1H) MS (ESI) m/z 328.0 (M+H)+.

후처리

  1. concentrationThe solution was concentrated
  2. additionTo the concentrate was added tetrahydrofuran (10 mL)
  3. concentrationwas continued in the 80° C. bath for 1 hour before concentration
  4. additionTo the concentrate was added dichloromethane (10 mL), methanol (1 mL) and HCl (4M in dioxane, 2 mL) Once LC/MS analysis
  5. concentrationwas concentrated
  6. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-f42cfc8f935f4c82be53a77dbee82471
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846663B2

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