1,1'-Carbonyldiimidazole → HCID 68751777, compound

HRID 346933

Reaction equation

HRID 346933 reaction equation
[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]

Participants

7

Reactant 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

Product 1

HCID 68751777HCID 68751777, compoundYield 71.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4540fd76ce904cbea39aec4940a6e47c
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Linked notes

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