1,1'-Carbonyldiimidazole → HCID 68751777、化合物

HRID 346933

反応式

HRID 346933 の反応式
[C:1]([O:5][C:6]([NH:8][CH:9]1[C:27](=[O:28])[N:26]2[CH:22]([CH2:23][CH:24]([O:29][C:30]3[C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[CH:33]=[CH:32][N:31]=3)[CH2:25]2)[C:21](=[O:40])[NH:20][C:19]2([C:41](O)=[O:42])[CH:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:56]([S:59]([NH2:62])(=[O:61])=[O:60])([CH3:58])[CH3:57].C1CCN2C(=NCCC2)CC1>C1COCC1.CO.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[C:27](=[O:28])[N:26]2[CH:22]([CH2:23][CH:24]([O:29][C:30]3[C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[CH:33]=[CH:32][N:31]=3)[CH2:25]2)[C:21](=[O:40])[NH:20][C:19]2([C:41]([NH:62][S:59]([CH:56]([CH3:58])[CH3:57])(=[O:61])=[O:60])=[O:42])[CH:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 3549191Propane-2-sulfonamideHCID 7242743414-Tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid

生成物 1

HCID 68751777HCID 68751777、化合物収率 71.6%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid (67 mg, 0.10 mmol) was dissolved in 5 mL of THF and treated with CDI (21 mg, 0.13 mmol). (Care was taken to avoid moisture by using oven dried glassware and maintaining a dry N2 atmosphere.) After refluxing the reaction mixture for one hour, it was cooled to rt and treated sequentially with isopropylsulfonamide (16 mg, 0.13 mmol) and DBU (20 mg, 0.13 mmol). After stirring for 24 h at rt, the THF was removed by rotary evaporation. The residue was partitioned between ethyl acetate and pH 4 buffer. The organic phase was dried (MgSO4) and concentrated in vacuo to give the crude product. Flash chromatography (1–5% MeOH/methylene chloride) gave 50 mg (71%) of the desired product. Further purification by preparative HPLC (YMC ODS-A, S5, 20×100 mm, gradient: 60% to 100% B) gave 30 mg (43%) of [18-(isoquinolin-1-yloxy)-2,15-dioxo-4-(propane-2-sulfonylaminocarbonyl)-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester as a white powder: 1H NMR (300 MHz, CD3Cl3) δ 1.22 (S, 9H), 1.31 (d. J=6.6 Hz, 3H), 1.41 (d, J=6.9 Hz, 3H), 1.20–1.96 (m, 11H), 2.30 (q, J=8.4 Hz, 1H), 2.56 (m, 1H), 2.69 (m, 2H), 3.69 (m, 1H), 4.03 (m, 1H), 4.29 (m, 1H), 4.62 (m, 2H), 4.97–5.06 (m, 2H), 5.68 (q, J=9.5 Hz, 1H), 5.91 (s, 1H), 6.76 (s, 1H), 7.23 (m, 1H), 7.45 (t, J=7.7 Hz, 1H), 7.63 (t, J=8.1 Hz, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.97 (d, J=5.9 Hz, 1H), 8.17 (d, J=8.1 Hz, 1H), 9.89 (s, 1H). LC-MS (Method A, retention time: 3.79 min), MS m/z 670 (M++1).

後処理

  1. customdried glassware
  2. temperaturemaintaining a dry N2 atmosphere
  3. temperature) After refluxing the reaction mixture for one hour
  4. customthe THF was removed by rotary evaporation
  5. customThe residue was partitioned between ethyl acetate and pH 4 buffer
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give the crude product

出典と根拠

ORDレコード
ord-4540fd76ce904cbea39aec4940a6e47c
出典データセット
uspto-grants-2007_02
特許番号
US07173004B2

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