2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 71550937, compound

HRID 1050879Notes

Reaction equation

HRID 1050879 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][CH2:73][CH2:74][O:75][C:76]5[C:77]([O:104][CH3:105])=[CH:78][C:79]6[C:85](=[O:86])[N:84]7[CH:87]=[C:88]([C:90]8[CH:95]=[CH:94][C:93]([O:96][CH2:97][CH2:98][CH2:99][N:100]([CH3:102])[CH3:101])=[CH:92][CH:91]=8)[CH2:89][C@H:83]7[CH:82]=[N:81][C:80]=6[CH:103]=5)[C:65]([O:67][CH3:68])=[CH:66][C:59]=4[C:58](=[O:106])[N:57]3[CH:107]=2)=[CH:50][CH:49]=1>CO.ClCCl>[CH3:102][N:100]([CH3:101])[CH2:99][CH2:98][CH2:97][O:96][C:93]1[CH:92]=[CH:91][C:90]([C:88]2[CH2:89][C@H:83]3[CH:82]=[N:81][C:80]4[CH:103]=[C:76]([O:75][CH2:74][CH2:73][CH2:72][CH2:71][CH2:70][O:69][C:64]5[C:65]([O:67][CH3:68])=[CH:66][C:59]6[C:58](=[O:106])[N:57]7[CH:107]=[C:54]([C:51]8[CH:50]=[CH:49][C:48]([NH:47][C:26](=[O:28])[C@@H:24]([NH:23][C:18](=[O:20])[C@@H:14]([NH:13][C:11](=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][N:5]9[C:1](=[O:22])[CH:2]=[CH:3][C:4]9=[O:21])[CH:15]([CH3:16])[CH3:17])[CH3:25])=[CH:53][CH:52]=8)[CH2:55][C@H:56]7[CH:62]=[N:61][C:60]=6[CH:63]=5)[C:77]([O:104][CH3:105])=[CH:78][C:79]=4[C:85](=[O:86])[N:84]3[CH:87]=2)=[CH:95][CH:94]=1

Participants

6

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 89501167HCID 89501167, compoundHCID 117611625HCID 117611625, compound

Product 1

HCID 71550937HCID 71550937, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A flame-dried flask was charged with maleimidocaproyl-valine-alanine linker (Compound 36 in Example 13 of WO 2011/130613 A1) (9 mg, 24 μmol, 1.5 eq) dissolved in 0.33 mL of 5% methanol in anhydrous dichloromethane. The acid was pre-activated by addition of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (7.1 mg, 29 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 17 (13 mg, 16 μmol, 1 eq). The reaction was stirred for 7 h 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 19 (5.1 mg, 27%). LC-MS: tR 9.09 min, m/z (ES+) found 1188.4 (M+H)+.

Workup

  1. additionThe activated acid was then added to a flame-dried flask
  2. stirringThe reaction was stirred for 7 h 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-4f9f38e210ea40bba0a16db8a08e1c79
Source dataset
uspto-grants-2016_07
Patent number
US09387258B2

Reaction notes

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