2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-((S)-7-methoxy-8-(3-(((S)-7-methoxy-2-methyl-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-2-yl)phenyl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide

HRID 2364954Notes

Reaction equation

HRID 2364954 reaction equation
[O:1]=[C:2]1[CH:6]=[CH:5][C:4](=[O:7])[N:3]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([NH:15][C@@H:16]([CH:25]([CH3:27])[CH3:26])[C:17]([NH:19][C@@H:20]([CH3:24])[C:21]([OH:23])=O)=[O:18])=[O:14].CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1.[NH2:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[CH2:54][C@@H:55]3[N:61]([CH:62]=2)[C:60](=[O:63])[C:59]2[CH:64]=[C:65]([O:91][CH3:92])[C:66]([O:68][CH2:69][CH2:70][CH2:71][O:72][C:73]4[C:88]([O:89][CH3:90])=[CH:87][C:76]5[C:77](=[O:86])[N:78]6[CH:84]=[C:83]([CH3:85])[CH2:82][C@H:79]6[CH:80]=[N:81][C:75]=5[CH:74]=4)=[CH:67][C:58]=2[N:57]=[CH:56]3)=[CH:49][CH:48]=1>CO.ClCCl>[O:7]=[C:4]1[CH:5]=[CH:6][C:2](=[O:1])[N:3]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([NH:15][C@@H:16]([CH:25]([CH3:27])[CH3:26])[C:17]([NH:19][C@@H:20]([CH3:24])[C:21]([NH:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[CH2:54][C@@H:55]3[N:61]([CH:62]=2)[C:60](=[O:63])[C:59]2[CH:64]=[C:65]([O:91][CH3:92])[C:66]([O:68][CH2:69][CH2:70][CH2:71][O:72][C:73]4[C:88]([O:89][CH3:90])=[CH:87][C:76]5[C:77](=[O:86])[N:78]6[CH:84]=[C:83]([CH3:85])[CH2:82][C@H:79]6[CH:80]=[N:81][C:75]=5[CH:74]=4)=[CH:67][C:58]=2[N:57]=[CH:56]3)=[CH:49][CH:48]=1)=[O:23])=[O:18])=[O:14]

Participants

5

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 53491734(S)-2-(4-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-methyl-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)propoxy)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5(11aH)-oneHCID 67452206(S)-2-((S)-2-(6-(2,5-dioxo-2H-pyrrol-1(5H)-yl)hexanamido)-3-methylbutanamido)propanoic acid

Product 1

HCID 534917366-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-((S)-7-methoxy-8-(3-(((S)-7-methoxy-2-methyl-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-2-yl)phenyl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamideYield 50%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a mixture of carboxylic acid 23 (8 mg, 21 umol) in 5% methanol/dichloromethane was added EEDQ (6.1 mg, 24.6 umol) and the mixture was stirred for 15 minutes under nitrogen at an ambient temperature. The resulting mixture was added to 11 (12 mg, 18.9 umol) and stirred for 3 hours under nitrogen. The reaction mixture was aspirated directly onto a 1 mm radial chromatotron plate and eluted with a gradient of 1 to 4% methanol in dichloromethane. Product containing fractions were concentrated under reduced pressure to give 9.4 mg (50%) of 30 as a yellow solid: MS (ES−) m/z 997.18 (M+H)+.

Workup

  1. stirringstirred for 3 hours under nitrogen
  2. washeluted with a gradient of 1 to 4% methanol in dichloromethane
  3. additionProduct containing fractions
  4. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-7ac545d9b94b418b801915763821424d
Source dataset
uspto-grants-2014_04
Patent number
US08697688B2

Reaction notes

Loading…