1,1'-Carbonyldiimidazole → N-[17-[2-ethoxy-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl] (cyclo-propyl)sulfonamide

HRID 2203467Notes

Reaction equation

HRID 2203467 reaction equation
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([O:14][CH:15]2[CH2:32][CH:31]3[CH:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]4[C:28]([C:34](O)=[O:35])([NH:29][C:30]3=[O:33])[CH2:27]4)[CH2:16]2)[C:11]2[C:6](=[C:7]([CH3:41])[C:8]([O:39][CH3:40])=[CH:9][CH:10]=2)[N:5]=1)[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:54]1([S:57]([NH2:60])(=[O:59])=[O:58])[CH2:56][CH2:55]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([O:14][CH:15]2[CH2:32][CH:31]3[CH:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]4[C:28]([C:34]([NH:60][S:57]([CH:54]5[CH2:56][CH2:55]5)(=[O:59])=[O:58])=[O:35])([NH:29][C:30]3=[O:33])[CH2:27]4)[CH2:16]2)[C:11]2[C:6](=[C:7]([CH3:41])[C:8]([O:39][CH3:40])=[CH:9][CH:10]=2)[N:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 6869453817-[2-Ethoxy-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

Product 1

HCID 68696188N-[17-[2-ethoxy-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl] (cyclo-propyl)sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2) (182 mg, 0.32 mmol) and CDI (139 mg, 0.29 mmol) in dry THF (10 mL) was heated at reflux for 1.5h under nitrogen. LCMS analysis showed one peak of the intermediate (2-1) (a stable intermediate, which can be isolated by purification on silica gel). The reaction mixture was cooled to room temperature and cyclopropyl-sulfonamide (93 mg, 0.76 mmol) was added. Then, DBU (138 mg, 0.91 mmol) was added. The reaction mixture was stirred at room temperature for 1 h, then heated at 55° C. for 12 h. Next, the solvent was evaporated, and the residue partitioned between ethyl acetate and acidic water (pH=3). The organic layer was dried (Na2SO4) and evaporated. The crude material was purified by column chromatography (ethyl acetate/CH2Cl2, 1:9). The residue was sonicated in water for 1 h, filtered off and washed with isopropylether to give the title product (3) as a white powder: m/z=669 (M+H)+. 1H NMR (CDCl3): 0.90-1.30 (m, 5H), 1.31-1.52 (m, 6H), 1.61-1.72 (m, 1H), 1.73-1.99 (m, 3H), 2.09-2.20 (m, 1H), 2.30-2.42 (m, 2H), 2.48-2.62 (m, 5H), 2.70-2.83 (m, 1H), 3.01 (s, 3H), 3.30-3.41 (m, 2H), 3.94 (s, 3H), 4.50-4.73 (m, 3H), 5.05 (t, J=10.0 Hz, 2H), 5.62-5.69 (m, 1H), 5.95 (s, 1H), 6.35 (br s, 1H), 7.01 (d, J=9.1 Hz, 1H), 7.85 (d, J=9.1 Hz, 1H), 10.8 (br s, 1H).

Workup

  1. temperaturewas heated
  2. customcan be isolated by purification on silica gel)
  3. temperatureheated at 55° C. for 12 h
  4. customNext, the solvent was evaporated
  5. customthe residue partitioned between ethyl acetate and acidic water (pH=3)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. customevaporated
  8. customThe crude material was purified by column chromatography (ethyl acetate/CH2Cl2, 1:9)
  9. customThe residue was sonicated in water for 1 h
  10. filtrationfiltered off
  11. washwashed with isopropylether

Sources & evidence

ORD record
ord-7fb1dfa7a72c4443856bca3c4e737809
Source dataset
uspto-grants-2016_06
Patent number
US09365582B2

Reaction notes

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