2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → 1-(2-iodoacetamido)-N-((S)-1-((S)-1-((E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)allylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-3,6,9,12-tetraoxapentadecan-15-amide

HRID 1057085Notes

Reaction equation

HRID 1057085 reaction equation
C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C.[NH2:19][C@@H:20]([CH:74]([CH3:76])[CH3:75])[C:21]([NH:23][C@@H:24]([CH3:73])[C:25]([NH:27][CH2:28]/[CH:29]=[CH:30]/[C:31]1[CH2:32][C@H:33]2[CH:39]=[N:38][C:37]3[CH:40]=[C:41]([O:46][CH2:47][CH2:48][CH2:49][O:50][C:51]4[C:52]([O:69][CH3:70])=[CH:53][C:54]5[C:60](=[O:61])[N:59]6[CH:62]=[C:63](/[CH:65]=[CH:66]/[CH3:67])[CH2:64][C@H:58]6[CH:57]=[N:56][C:55]=5[CH:68]=4)[C:42]([O:44][CH3:45])=[CH:43][C:36]=3[C:35](=[O:71])[N:34]2[CH:72]=1)=[O:26])=[O:22].[I:77][CH2:78][C:79](=[O:98])[NH:80][CH2:81][CH2:82][O:83][CH2:84][CH2:85][O:86][CH2:87][CH2:88][O:89][CH2:90][CH2:91][O:92][CH2:93][CH2:94][C:95](O)=[O:96]>ClCCl>[I:77][CH2:78][C:79]([NH:80][CH2:81][CH2:82][O:83][CH2:84][CH2:85][O:86][CH2:87][CH2:88][O:89][CH2:90][CH2:91][O:92][CH2:93][CH2:94][C:95]([NH:19][C@@H:20]([CH:74]([CH3:76])[CH3:75])[C:21]([NH:23][C@@H:24]([CH3:73])[C:25]([NH:27][CH2:28]/[CH:29]=[CH:30]/[C:31]1[CH2:32][C@H:33]2[CH:39]=[N:38][C:37]3[CH:40]=[C:41]([O:46][CH2:47][CH2:48][CH2:49][O:50][C:51]4[C:52]([O:69][CH3:70])=[CH:53][C:54]5[C:60](=[O:61])[N:59]6[CH:62]=[C:63](/[CH:65]=[CH:66]/[CH3:67])[CH2:64][C@H:58]6[CH:57]=[N:56][C:55]=5[CH:68]=4)[C:42]([O:44][CH3:45])=[CH:43][C:36]=3[C:35](=[O:71])[N:34]2[CH:72]=1)=[O:26])=[O:22])=[O:96])=[O:98]

Participants

5

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 872435891-Iodo-2-oxo-6,9,12,15-tetraoxa-3-azaoctadecan-18-oic acidHCID 90408320(S)-2-amino-N-((S)-1-((E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)allylamino)-1-oxopropan-2-yl)-3-methylbutanamide

Product 1

HCID 904080301-(2-iodoacetamido)-N-((S)-1-((S)-1-((E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)allylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-3,6,9,12-tetraoxapentadecan-15-amideYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (0.007 g, 0.0290 mmol, 1.0 eq) was added to a solution of amine 20c (assumed 100%, 0.023 g, 0.0290 mmol, 1.0 eq) and 1-iodo-2-oxo-6,9,12,15-tetraoxa-3-azaoctadecan-18-oic acid (I5)(0.0126 g, 0.0290 mmol, 1.0 eq) in dry dichloromethane (2 mL). The reaction mixture was stirred for 18 hours, then diluted with DCM (6 mL) and washed with water (2×10 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was subjected to flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 5:1 v/v DCM/MeOH) to afford the product as a pale yellow oil (0.0043 g, 29%). LC/MS (2.380 min (ES+)), m/z: 605.0 ½[M+2H]+.

Workup

  1. washwashed with water (2×10 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-373c80d943914826bc966ae19280a5cd
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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