Cesium carbonate → 2-[1-(4-(Ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(1,1-dimethylethoxycarbonyl)propyl]aminocarbonyl-7-methyl-4-(1-(ethoxycarbonyl)cyclobut-1-oxy)quinoline

HRID 1795223Notes

Reaction equation

HRID 1795223 reaction equation
[CH2:1]([O:3][C:4]([C:6]1(Br)[CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH2:11]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([CH:24]([NH:34][C:35]([C:37]2[CH:46]=[C:45]([OH:47])[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:38]=2)=[O:36])[CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:23])[CH2:18][CH2:17]1)=[O:15])[CH3:12].[C:48](=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:11]([O:13][C:14]([N:16]1[CH2:17][CH2:18][N:19]([C:22]([CH:24]([NH:34][C:35]([C:37]2[CH:46]=[C:45]([O:47][C:6]3([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:9][CH2:8][CH2:7]3)[C:44]3[C:39](=[CH:40][C:41]([CH3:48])=[CH:42][CH:43]=3)[N:38]=2)=[O:36])[CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:23])[CH2:20][CH2:21]1)=[O:15])[CH3:12]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 97595Ethyl 1-bromocyclobutanecarboxylate2×HCID 178473368HCID 178473368, compound

Product 1

HCID 221848412-[1-(4-(Ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(1,1-dimethylethoxycarbonyl)propyl]aminocarbonyl-7-methyl-4-(1-(ethoxycarbonyl)cyclobut-1-oxy)quinolineYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Ethoxycarbonyl-1-bromocyclobutane (0.62 g, 3.03 mmol) was added to a solution of 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(1,1-dimethylethoxycarbonyl)propyl]aminocarbonyl-4-hydroxyquinoline (0.8 g, 1.52 mmol) and cesium carbonate (1.00 g, 3.03 mmol) in N,N-dimethylformamide (DMF) (15 mL) and stirred at 90–100° C. At every 2 hours, excess equimolar amounts of 1-ethoxycarbonyl-1-bromocyclobutane and cesium carbonate were added to the solution to a total of 8 equivalents of each reagent. After 10 hours, the reaction mixture was filtered, the solvent was evaporated and the residue was purified by preparative HPLC to afford 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(1,1-dimethylethoxycarbonyl)propyl]aminocarbonyl-7-methyl-4-(1-(ethoxycarbonyl)cyclobut-1-oxy)quinoline (0.45 g , 38%) as a white solid (TFA salt); NMR (DMSO-d6) 1.04 (t, 3), 1.14 (t, 3), 1.32 (s, 9), 1.82 (m, 1), 2.00 (m, 3), 2.26 (m, 2), 2.52 (s, 3), 2.58 (m, 2), 2.78 (m, 2), 3.5 (m, 8), 4.04 (q, 2), 4.15 (q, 2), 5.00 (m, 1), 6.94 (s, 1), 7.52 (d, 1), 7.88 (s, 1), 8.14 (d, 1), 8.84 (d, 1) ppm.

Workup

  1. waitAfter 10 hours
  2. filtrationthe reaction mixture was filtered
  3. customthe solvent was evaporated
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-df5d6ae258db4a46b277f0936757474e
Source dataset
uspto-grants-2006_04
Patent number
US07026323B2

Reaction notes

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