1,1'-Carbonyldiimidazole → N-[17-[7-methoxy-8-methyl-2-(thiazol-2-yl)quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide

HRID 402139Notes

Reaction equation

HRID 402139 reaction equation
[CH3:1][O:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39](O)=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)=[CH:8][C:9]([C:14]3[S:15][CH:16]=[CH:17][N:18]=3)=[N:10]2)=[CH:5][CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:56]1([S:59]([NH2:62])(=[O:61])=[O:60])[CH2:58][CH2:57]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[CH3:1][O:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:62][S:59]([CH:56]6[CH2:58][CH2:57]6)(=[O:61])=[O:60])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)=[CH:8][C:9]([C:14]3[S:15][CH:16]=[CH:17][N:18]=3)=[N:10]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418Cyclopropanesulfonamide2×HCID 6687080717-[7-Methoxy-8-methyl-2-(thiazol-2-yl)quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

Product 1

HCID 66887288N-[17-[7-methoxy-8-methyl-2-(thiazol-2-yl)quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 29 (85 mg, 0.14 mmol) and CDI (47 mg, 0.29 mmol) in dry THF (7 mL) is heated at reflux for 2 h under nitrogen. LCMS analysis shows one peak of the intermediate (RT=5.37). The reaction mixture is cooled to room temperature and cyclopropylsulfonamide (52 mg, 0.43 mmol) is added. Then, DBU (50 μL, 0.33 mmol) is added and the reaction mixture is stirred at room temperature for 1 h, and then heated at 55° C. for 24 h. Solvent is evaporated, and the residue partitioned between AcOEt and acidic water (pH=3). The crude material is purified by column chromatography (AcOEt/CH2Cl2/Petroleum ether, 1:1:1). The residue is crystallized in Et2O, filtered to give the target compound contaminated with the cyclopropyl-sulfonamide. This material is triturated in 3 ml of water, filtered, washed with water and dried overnight in the high vacuum pump to give the target compound 30 as a white powder: m/z=708 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 2 h under nitrogen
  3. customone peak of the intermediate (RT=5.37)
  4. temperatureheated at 55° C. for 24 h
  5. customSolvent is evaporated
  6. customthe residue partitioned between AcOEt and acidic water (pH=3)
  7. customThe crude material is purified by column chromatography (AcOEt/CH2Cl2/Petroleum ether, 1:1:1)
  8. customThe residue is crystallized in Et2O
  9. filtrationfiltered
  10. customto give the target compound
  11. customThis material is triturated in 3 ml of water
  12. filtrationfiltered
  13. washwashed with water
  14. customdried overnight in the high vacuum pump

Sources & evidence

ORD record
ord-060f86874dbc443c832f9114667afe7e
Source dataset
uspto-grants-2014_06
Patent number
US08741926B2

Reaction notes

Loading…