2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 89508724, compound

HRID 1050884Notes

Reaction equation

HRID 1050884 reaction equation
[C:1]1(=[O:22])[N:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([NH:13][C@H:14]([C:18]([OH:20])=O)[CH:15]([CH3:17])[CH3:16])=[O:12])[C:4](=[O:21])[CH:3]=[CH:2]1.[NH2:23][C@H:24]([C:26]([OH:28])=O)[CH3:25].C(OC(N1C2C(=CC=CC=2)C=CC1OCC)=O)C.[NH2:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH2:55][C@H:56]3[CH:62]=[N:61][C:60]4[CH:63]=[C:64]([O:69][CH2:70][CH2:71][CH2:72][O:73][C:74]5[C:75]([O:96][CH3:97])=[CH:76][C:77]6[C:83](=[O:84])[N:82]7[CH:85]=[C:86]([C:88]8[CH:93]=[CH:92][C:91]([OH:94])=[CH:90][CH:89]=8)[CH2:87][C@H:81]7[CH:80]=[N:79][C:78]=6[CH:95]=5)[C:65]([O:67][CH3:68])=[CH:66][C:59]=4[C:58](=[O:98])[N:57]3[CH:99]=2)=[CH:50][CH:49]=1>CO.ClCCl>[O:22]=[C:1]1[CH:2]=[CH:3][C:4](=[O:21])[N:5]1[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([NH:13][C@@H:14]([CH:15]([CH3:16])[CH3:17])[C:18]([NH:23][C@@H:24]([CH3:25])[C:26]([NH:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH2:55][C@H:56]3[CH:62]=[N:61][C:60]4[CH:63]=[C:64]([O:69][CH2:70][CH2:71][CH2:72][O:73][C:74]5[C:75]([O:96][CH3:97])=[CH:76][C:77]6[C:83](=[O:84])[N:82]7[CH:85]=[C:86]([C:88]8[CH:89]=[CH:90][C:91]([OH:94])=[CH:92][CH:93]=8)[CH2:87][C@H:81]7[CH:80]=[N:79][C:78]=6[CH:95]=5)[C:65]([O:67][CH3:68])=[CH:66][C:59]=4[C:58](=[O:98])[N:57]3[CH:99]=2)=[CH:50][CH:49]=1)=[O:28])=[O:20])=[O:12]

Participants

6

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 71553880HCID 71553880, compoundHCID 89501167HCID 89501167, compound

Product 1

HCID 89508724HCID 89508724, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A flame-dried flask was charged with maleimidocaproyl-valine-alanine linker (Compound 36 of Example 13 in WO 2011/130613 A1) (11 mg, 29 μmol, 1.5 eq) dissolved in 0.8 mL of 5% methanol in anhydrous dichloromethane. The acid was pre-activated by addition of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (9 mg, 34 μmol, 1.8 eq), followed by stirring at room temperature under nitrogen for 15 minutes. The activated acid was then added to a flame-dried flask containing PBD dimer 14 (13 mg, 19 μmol, 1 eq). The reaction was stirred for 4 hours at room temperature under nitrogen, at which time LC-MS revealed conversion to product. The material was diluted in dichloromethane and purified by radial chromatography on a 1 mm chromatotron plate eluted with CH2Cl2/MeOH mixtures (100:0 to 80:20) to provide 15 (7.7 mg, 38%). LC-MS: m/z (ES+) found 1075.5 (M+H)+.

Workup

  1. additionThe activated acid was then added to a flame-dried flask
  2. stirringThe reaction was stirred for 4 hours at room temperature under nitrogen, at which time LC-MS
  3. custompurified by radial chromatography on a 1 mm chromatotron plate
  4. washeluted with CH2Cl2/MeOH mixtures (100:0 to 80:20)

Sources & evidence

ORD record
ord-7e403174449243a9a21f22079acb257e
Source dataset
uspto-grants-2016_07
Patent number
US09387259B2

Reaction notes

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