1,2-Dichloroethane → N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide

HRID 857771노트

반응식

HRID 857771 반응식
C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([N:39]2[CH:43]=[N:42][N:41]=[N:40]2)=[C:28]([CH:38]=1)[CH2:29][NH:30][C:31](=[O:37])[C@@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1.[C:44]([O:48][C:49]([N:51]1[CH2:54][CH2:53][C:52]1([CH3:58])[C:55](O)=[O:56])=[O:50])([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C>[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([N:39]2[CH:43]=[N:42][N:41]=[N:40]2)=[C:28]([CH:38]=1)[CH2:29][NH:30][C:31](=[O:37])[C@@H:32]1[CH2:36][CH2:35][CH2:34][N:33]1[C:55]([C:52]1([CH3:58])[CH2:53][CH2:54][N:51]1[C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])=[O:56]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 218663321-[(Tert-butoxy)carbonyl]-2-methylazetidine-2-carboxylic acidHCID 69656419N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide hydrochloride

생성물 1

HCID 69656015N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

EDC (0.104 g, 0.54 mmol), HOAt (24.6 mg, 0.18 mmol), NMM (0.079 mL, 0.72 mmol), and N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide hydrochloride (Example 26, Step B, 0.143 g, 0.42 mmol) were added to a stirred solution of racemic 1-(tert-butoxycarbonyl)-2-methylazetidine-2-carboxylic acid (0.143 g, 0.36 mmol in DMF (1.1 mL). After 3 h at room temperature the reaction was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The two diastereomers were separated and purified by reverse phase HPLC. The more polar diastereomer was concentrated in vacuo. N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide (diastereomer A) was obtained as a glass. MS m/z=404.6).

후처리

  1. customAfter 3 h at room temperature the reaction was partitioned between EtOAc and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe two diastereomers were separated
  6. custompurified by reverse phase HPLC
  7. concentrationThe more polar diastereomer was concentrated in vacuo

출처 및 근거

ORD 기록
ord-8781b70d0e0f4e7eb12b04d282b9cb0c
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07144899B2

반응 노트

불러오는 중…