Triphenylphosphine → (2S,4S)-1-tert-Butyl 2-methyl 4-(((S)-2-(tert-butoxycarbonyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 339244노트

반응식

HRID 339244 반응식
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C@@H:7]([C:19](=[O:31])[NH:20][C@H:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][CH2:23][CH2:22]3)[N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O[C@H:52]1[CH2:56][N:55]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@H:54]([C:64]([O:66][CH3:67])=[O:65])[CH2:53]1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C(Cl)Cl>[C:15]([O:14][C:12]([N:8]1[C@H:7]([C:19](=[O:31])[NH:20][C@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23][CH2:22]2)[CH2:6][C:5]2[C:10](=[CH:11][C:2]([O:1][C@@H:52]3[CH2:56][N:55]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@H:54]([C:64]([O:66][CH3:67])=[O:65])[CH2:53]3)=[CH:3][CH:4]=2)[CH2:9]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 730421,1'-(Azodicarbonyl)dipiperidine2회HCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester2회HCID 86705863(S)-tert-Butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate2회

생성물 1

HCID 86705879(2S,4S)-1-tert-Butyl 2-methyl 4-(((S)-2-(tert-butoxycarbonyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)pyrrolidine-1,2-dicarboxylate수율 86%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of (S)-tert-butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound D of Example 1, 50 mg, 0.12 mmol) in CH2Cl2 (1.0 mL) was added PPh3 (37 mg, 0.14 mmol), (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (Aldrich, 35 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol). The resulting reaction mixture was allowed to stir overnight at room temperature. Additional (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (35 mg, 0.14 mmol), PPh3 (37 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol) were then added. The reaction mixture was allowed to stir at room temperature for 60 h, then concentrated in vacuo and purified using flash column chromatography (gradient from 0% to 60% EtOAc/hexanes) to give the title compound (66 mg, 86%) as a colorless oil. MS (ESI+) m/z 650.4 (M+H)+.

후처리

  1. customThe resulting reaction mixture
  2. stirringto stir at room temperature for 60 h
  3. concentrationconcentrated in vacuo
  4. custompurified

출처 및 근거

ORD 기록
ord-8e4d901c20154ca5877e75cb2596283a
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889712B2

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