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Hydrochloric Acid → 1-{[1-(2-Methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid

HRID 719845
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HRID 719845 반응식
C([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:21]=3)[CH2:16][N:15]2[C:38](=[O:49])[CH:39]([NH:44][C:45]([O:47][CH3:48])=[O:46])[C:40]([CH3:43])([CH3:42])[CH3:41])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])C.O.[OH-].[Li+].Cl>C1COCC1.CO.O>[CH3:48][O:47][C:45]([NH:44][CH:39]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:38]([N:15]1[CH2:16][CH:17]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=3)[N:23]=[C:22]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:21]=2)[CH2:18][CH:14]1[C:12]([NH:11][C:6]1([C:4]([OH:5])=[O:3])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:13])=[O:49])=[O:46]
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참가 물질

7

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 666700711-{[1-(2-Methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

생성물 1

HCID 219010671-{[1-(2-Methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid
수율 69%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 1-{[1-(2-methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropane-carboxylic acid ethyl ester (410 mg, 0. 52 mmol) in THF (20 mL), methanol (11.5 mL) and water (3.8 mL) mixture, lithium hydroxide monohydrate (328 mg, 7.82 mmol) was added. The reaction mixture was stirred at rt for overnight. Then it was acidified with 1N HCl solution and concentrated. The residue was extracted with EtOAc twice and the organic layers were combined. Then it was dried (MgSO4) and concentrated to give an off-white solid. (230 mg, 69% yield). 1H NMR (400 MHz, CD3OD) δ 1.02 (s, 9H), 1.43 (dd, J=9.54, 5.14 Hz, 1H), 1.68 (dd, J=8.07, 5.14 Hz, 1H), 2.17 (m, 1H), 2.57 (m, 1H), 2.75 (m, 1H), 3.34 (s, 3H), 4.03 (s, 3H), 4.06 (m, 1H), 4.18 (s, 1H), 4.60–4.70 (m, 2H), 4.88 (m, 1H), 5.08 (dd, J=10.39, 1.59 Hz, 1H), 5.25 (dd, J=17.36, 1.71 Hz, 1H), 5.77–5.87 (m, 2H) 7.38 (dd, J=9.29, 2.20 Hz, 1H), 7.50 (m, 1H), 7.62 (m, 1H), 7.69–7.78 (m, 3H), 8.03–8.07 (m, 2H), 8.36 (d, J=9.20 Hz, 1H). LC-MS (retention time: 2.177 min.), MS m/z 645 (MH+).

후처리

  1. concentrationconcentrated
  2. extractionThe residue was extracted with EtOAc twice
  3. dry with materialThen it was dried (MgSO4)
  4. concentrationconcentrated
  5. customto give an off-white solid

출처 및 근거

ORD 기록
ord-87e61a73ce004b5b9b67768647a17429
출처 데이터셋
uspto-grants-2006_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07132504B2

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