Methanol → 14-Tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid

HRID 346955노트

반응식

HRID 346955 반응식
C([O:3][C:4]([C:6]12[CH2:24][CH:23]1[CH:22]=[CH:21][CH2:20][O:19][CH2:18][CH2:17][CH2:16][CH:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:14](=[O:33])[N:13]1[CH:9]([CH2:10][CH:11]([O:34][C:35]3[C:44]4[C:39](=[CH:40][C:41]([O:45][CH3:46])=[CH:42][CH:43]=4)[CH:38]=[CH:37][N:36]=3)[CH2:12]1)[C:8](=[O:47])[NH:7]2)=[O:5])C.O.CO.[OH-].[Li+]>C1COCC1.CO.C(Cl)(Cl)Cl>[C:29]([O:28][C:26]([NH:25][CH:15]1[C:14](=[O:33])[N:13]2[CH:9]([CH2:10][CH:11]([O:34][C:35]3[C:44]4[C:39](=[CH:40][C:41]([O:45][CH3:46])=[CH:42][CH:43]=4)[CH:38]=[CH:37][N:36]=3)[CH2:12]2)[C:8](=[O:47])[NH:7][C:6]2([C:4]([OH:5])=[O:3])[CH:23]([CH2:24]2)[CH:22]=[CH:21][CH2:20][O:19][CH2:18][CH2:17][CH2:16]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

참가 물질

7

반응물 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 6874824914-Tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid ethyl ester2회

생성물 1

HCID 6875130114-Tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid수율 70%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 21584188Chloroform methanol용매

실험 절차

To a solution of 14-tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid ethyl ester (the product of step 26G, 667 mg, 1.02 mmol) in 25.7 ml of THF was added 2.9 ml of water, 11.4 ml of methanol, and powdered lithium hydroxide (489 mg, 20.4 mmol). The reaction mixture was stirred at rt for 6 h, and then concentrated in vacuo. The residue was partitioned between ethyl acetate and 20.4 ml of 1 N aq. HCl. To the resulting solution was added pH 4 buffer (biphthalate). The organic phase was washed with water, sat. aq. NaCl, dried (MgSO4), and concentrated in vacuo to give the crude product. Flash chromatography (silica gel, 0–10% methanol/chloroform) gave 446 mg (˜70%) of 14-tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid as a slightly pink collapsed foam: 1H NMR (500 MHz, METHANOL-D4) δ 0.99–1.16 (m, 1H), 1.22 (s, 9H), 1.50–2.04 (m, 6H), 2.40–2.73 (m, 3H), 3.41–3.50 (m, 1H), 3.51–3.62 (m, 1H), 3.73–3.86 (m, 1H), 3.90 (s, 3H), 4.03 (d, J=10.52 Hz, 1H), 4.21 (d, J=8.31 Hz, 1H), 4.42–4.72 (m, 3H), 5.65 (s, 2H), 5.82 (s, 1H), 7.06 (d, J=9.05 Hz, 1H), 7.15 (s, 1H), 7.22 (d, J=5.87 Hz, 1H), 7.87 (m, J=9.29 Hz, 2H), 8.14 (d, J=8.56 Hz, 1H). LC-MS (Method B, retention time: 1.46 min), MS m/z 625 (M++1).

후처리

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and 20.4 ml of 1 N aq. HCl
  3. additionTo the resulting solution was added pH 4 buffer (biphthalate)
  4. washThe organic phase was washed with water, sat. aq. NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give the crude product

출처 및 근거

ORD 기록
ord-c25d5d1604bd4d6f8461b47059c23742
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173004B2

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