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 346955Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 346955
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]

Komponenten

7

Edukt 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 ester2×

Produkt 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 acidAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 21584188Chloroform methanolLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-c25d5d1604bd4d6f8461b47059c23742
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07173004B2

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