Urea → (7R,7aS)-4-(7-Hydroxy-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carbonitrile

HRID 501513

반응식

HRID 501513 반응식
CCN([CH:7]([CH3:9])C)C(C)C.[N:10]([C:13]1[C:22]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=2[C:16]([C:23]#[N:24])=[CH:15][CH:14]=1)=[C:11]=[O:12].NC(N)=[O:27].C1CCN2C(=NCCC2)CC1.[NH:40]1[CH2:46][C:44](=[O:45])N[C:41]1=O>C(Cl)Cl>[OH:27][C@H:7]1[C@@H:46]2[N:40]([C:11](=[O:12])[N:10]([C:13]3[C:22]4[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=4[C:16]([C:23]#[N:24])=[CH:15][CH:14]=3)[C:44]2=[O:45])[CH2:41][CH2:9]1

참가 물질

7

반응물 5

HCID 1176UreaHCID 10006HydantoinHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 597543044-Isocyanato-5,6,7,8-tetrahydronaphthalene-1-carbonitrile

생성물 1

HCID 9904811(7R,7aS)-4-(7-Hydroxy-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carbonitrile

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

To a suspension of compound 1E (0.145 g, 0.56 mmol) in CH2Cl2 (2 mL) cooled at 0° C. was added i-Pr2NEt (0.12 mL, 0.69 mmol). After stirring at 0° C. for 20 min, compound 2E (95 mg, 0.48 mmol) in CH2Cl2 (1 mL) solution was added, along with 4 Å molecular sieves (0.5 g) and the resulting mixture stirred at rt until urea formation was complete (˜2 h). To the mixture was then added DBU (0.15 mL, 1.0 mmol), the resulting brown colored suspension was stirred vigorously at rt until hydantoin formation was complete (˜15 h). The reaction mixture was loaded on a silica gel column, eluted with 40% EtOAc/hexane, and 5% MeOH in EtOAc/hexane (1:1) to afford 128 mg of the title compound as a white solid. HPLC: 99% at 2.42 min (retention time) (Conditions: Phenom. Luna C18 (4.6×50 mm); Eluted with 0% to 100% B; 4 min gradient (A=90% H2O-10% MeOH-0.1% H3PO4 and B=10% H2O-90% MeOH-0.1% H3PO4), Flow rate at 4 mL/min., UV detection at 220 nm). Chiral HPLC: retention time=9.01 min (99%); Conditions: (CHIRALPAK® OD column 4.6×250 mm; 25% isopropanol in hexane over 30 min at flow rate 1.0 mL/min, UV detection at 220 nm); MS (ES) m/z 312 [M+1]+

후처리

  1. custom(˜2 h)
  2. custom(˜15 h)
  3. washeluted with 40% EtOAc/hexane, and 5% MeOH in EtOAc/hexane (1:1)

출처 및 근거

ORD 기록
ord-5da9b7f508994665bc0d325b7430f09d
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772267B2

연결된 노트

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