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Triethylamine → (8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

HRID 572047
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HRID 572047 반응식
Cl.[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:22][N:15]4[C:16](=[O:21])[CH2:17][CH2:18][NH:19][CH2:20][C@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[F:30][C:31]([F:43])([F:42])[C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1.C(OCC)(=O)C>ClCCl>[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:22][N:15]4[C:16](=[O:21])[CH2:17][CH2:18][N:19]([S:38]([C:35]5[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:42])[F:43])=[CH:37][CH:36]=5)(=[O:40])=[O:39])[CH2:20][C@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1
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HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideHCID 86723197(8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride

생성물 1

HCID 76287412(8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one
수율 62%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

(8R,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (27.6 mg, 0.085 mmol, 1.0 equivalent, prepared as described in Example 55, Part B) was suspended in dichloromethane (1.0 mL) in a 4-mL scintillation vial. Triethylamine (43 mg, 0.425 mmol, 5.0 equivalents) was added followed by 4-(trifluoromethyl)benzene-1-sulfonyl chloride (27 mg, 0.11 mmol, 1.3 equivalents) as a solution in dichloromethane (0.1 mL). The reaction was stirred for 15 minutes. The mixture was loaded directly onto a 4 g silica gel column and with 0:100 to 50:50 ethyl acetate:heptanes (flow rate=18 mL/minute) over 20 minutes to give the title compound as a white solid (25 mg, 62%). 1H NMR (400 MHz, CDCl3) δ ppm 7.95 (d, J=1.4 Hz, 1H), 7.92 (d, J=1.4 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.82 (d, J=8.4 Hz, 2H), 5.53-5.25 (m, 1H), 4.17 (td, J=9.4, 3.0 Hz, 1H), 4.12-4.00 (m, 1H), 3.97 (d, J=13.4 Hz, 1H), 3.79 (d, J=3.5 Hz, 2H), 2.99-2.55 (m, 5H), 2.14-1.92 (m, 2H), 0.95 (ddt, J=12.1, 7.0, 2.0 Hz, 4H); MS (ESI+) m/z expected 497.1; found: 497.0 (M+H)+; [α]D24.1=0.19 (c=0.12, CH3OH).

출처 및 근거

ORD 기록
ord-0e12fe013a4747179a959558c26f6aef
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09029361B2

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