Piperidine → (S)-2-amino-N-((S)-1-((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)allylamino)-1-oxopropan-2-yl)-3-methylbutanamide

HRID 1057084Notes

Reaction equation

HRID 1057084 reaction equation
N1CCCCC1.[CH3:7][O:8][C:9]1[C:56]([O:57][CH2:58][CH2:59][CH2:60][O:61][C:62]2[C:63]([O:90][CH3:91])=[CH:64][C:65]3[C:71](=[O:72])[N:70]4[CH:73]=[C:74]([C:76]5[CH:81]=[CH:80][C:79]([N:82]6[CH2:87][CH2:86][N:85]([CH3:88])[CH2:84][CH2:83]6)=[CH:78][CH:77]=5)[CH2:75][C@H:69]4[CH:68]=[N:67][C:66]=3[CH:89]=2)=[CH:55][C:12]2[N:13]=[CH:14][C@@H:15]3[CH2:21][C:20](/[CH:22]=[CH:23]/[CH2:24][NH:25][C:26](=[O:54])[C@@H:27]([NH:29][C:30](=[O:53])[C@H:31]([NH:35]C(=O)OCC4C5C=CC=CC=5C5C4=CC=CC=5)[CH:32]([CH3:34])[CH3:33])[CH3:28])=[CH:19][N:16]3[C:17](=[O:18])[C:11]=2[CH:10]=1>CN(C=O)C.C(Cl)Cl>[NH2:35][C@@H:31]([CH:32]([CH3:34])[CH3:33])[C:30]([NH:29][C@@H:27]([CH3:28])[C:26]([NH:25][CH2:24]/[CH:23]=[CH:22]/[C:20]1[CH2:21][C@H:15]2[CH:14]=[N:13][C:12]3[CH:55]=[C:56]([O:57][CH2:58][CH2:59][CH2:60][O:61][C:62]4[C:63]([O:90][CH3:91])=[CH:64][C:65]5[C:71](=[O:72])[N:70]6[CH:73]=[C:74]([C:76]7[CH:81]=[CH:80][C:79]([N:82]8[CH2:83][CH2:84][N:85]([CH3:88])[CH2:86][CH2:87]8)=[CH:78][CH:77]=7)[CH2:75][C@H:69]6[CH:68]=[N:67][C:66]=5[CH:89]=4)[C:9]([O:8][CH3:7])=[CH:10][C:11]=3[C:17](=[O:18])[N:16]2[CH:19]=1)=[O:54])=[O:53]

Participants

5

Reactant 2

HCID 8082PiperidineHCID 131736463(9H-fluoren-9-yl)methyl(R)-1-((S)-1-((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)allylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate

Product 1

HCID 89500462(S)-2-amino-N-((S)-1-((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)allylamino)-1-oxopropan-2-yl)-3-methylbutanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Piperidine (0.058 mL, 0.590 mmol, 12.0 eq.) was added to a stirring mixture of Fmoc amine 19e (0.050 g, 0.0492 mmol, 1.0 eq.) in anhydrous DMF (0.8 mL) and the mixture was stirred at ambient temperature. After 20 minutes, LCMS showed reaction was completed so 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 to dryness under reduced pressure. Co-evaporation with n-hexanes afforded the product as a brown oil, and the material was not subjected to further purification (0.040 g, assumed 100%). LC/MS (1.533 min (ES+)), m/z: 928.2 [M+H]+.

Workup

  1. customreaction
  2. washwashed with water (3×30 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customCo-evaporation with n-hexanes

Sources & evidence

ORD record
ord-06d3c41520c74fa5b8471dfec63fcede
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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