(9H-fluoren-9-yl)methyl(E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-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)allylcarbamate → (S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(11aH)-one

HRID 1057074Notes

Reaction equation

HRID 1057074 reaction equation
[CH3:1][O:2][C:3]1[C:38]([O:39][CH2:40][CH2:41][CH2:42][O:43][C:44]2[C:45]([O:72][CH3:73])=[CH:46][C:47]3[C:53](=[O:54])[N:52]4[CH:55]=[C:56]([C:58]5[CH:63]=[CH:62][C:61]([N:64]6[CH2:69][CH2:68][N:67]([CH3:70])[CH2:66][CH2:65]6)=[CH:60][CH:59]=5)[CH2:57][C@H:51]4[CH:50]=[N:49][C:48]=3[CH:71]=2)=[CH:37][C:6]2[N:7]=[CH:8][C@@H:9]3[CH2:15][C:14](/[CH:16]=[CH:17]/[CH2:18][NH:19]C(=O)OCC4C5C=CC=CC=5C5C4=CC=CC=5)=[CH:13][N:10]3[C:11](=[O:12])[C:5]=2[CH:4]=1>N1CCCCC1.CN(C=O)C.C(Cl)Cl>[NH2:19][CH2:18]/[CH:17]=[CH:16]/[C:14]1[CH2:15][C@H:9]2[CH:8]=[N:7][C:6]3[CH:37]=[C:38]([O:39][CH2:40][CH2:41][CH2:42][O:43][C:44]4[C:45]([O:72][CH3:73])=[CH:46][C:47]5[C:53](=[O:54])[N:52]6[CH:55]=[C:56]([C:58]7[CH:63]=[CH:62][C:61]([N:64]8[CH2:65][CH2:66][N:67]([CH3:70])[CH2:68][CH2:69]8)=[CH:60][CH:59]=7)[CH2:57][C@H:51]6[CH:50]=[N:49][C:48]=5[CH:71]=4)[C:3]([O:2][CH3:1])=[CH:4][C:5]=3[C:11](=[O:12])[N:10]2[CH:13]=1

Participants

5

Reactant 1

HCID 131736457(9H-fluoren-9-yl)methyl(E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-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)allylcarbamate

Product 1

HCID 90407808(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(11aH)-oneYield 7%

Reagents, catalysts & solvents 3

HCID 8082PiperidineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Piperidine (4 drops, excess) was added to a stirring mixture of Fmoc allylamine 15e (0.02 g, 0.0204 mmol, 1.0 eq.) in anhydrous DMF (0.25 mL) and the mixture was stirred at ambient temperature. After 30 minutes, the reaction mixture was diluted with DCM (30 mL) and washed with water (3×30 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in chloroform and the resulting precipitate was collected by filtration to afford the product as an orange solid (0.001 g, 7%). LC/MS (1.495 min (ES+)), m/z: 379.5 ½[M+2H]+.

Workup

  1. washwashed with water (3×30 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe crude material was dissolved in chloroform
  6. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-c6f9e6fc44c044569a97123bf9cb7c2b
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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