Piperidine → (S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-10-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione

HRID 1057077Notes

Reaction equation

HRID 1057077 reaction equation
N1CCCCC1.[CH3:7][O:8][C:9]1[C:53]([O:54][CH2:55][CH2:56][CH2:57][O:58][C:59]2[C:60]([O:96][CH3:97])=[CH:61][C:62]3[C:68](=[O:69])[N:67]4[CH:70]=[C:71]([C:73]5[CH:78]=[CH:77][C:76]([N:79]6[CH2:84][CH2:83][N:82]([CH3:85])[CH2:81][CH2:80]6)=[CH:75][CH:74]=5)[CH2:72][C@H:66]4[C:65](=[O:86])[N:64]([CH2:87][O:88][CH2:89][CH2:90][Si:91]([CH3:94])([CH3:93])[CH3:92])[C:63]=3[CH:95]=2)=[CH:52][C:12]2[N:13]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:14](=[O:43])[C@@H:15]3[CH2:21][C:20](/[CH:22]=[CH:23]/[CH2:24][NH:25]C(=O)OCC4C5C=CC=CC=5C5C4=CC=CC=5)=[CH:19][N:16]3[C:17](=[O:18])[C:11]=2[CH:10]=1>CN(C=O)C.C(Cl)Cl>[NH2:25][CH2:24]/[CH:23]=[CH:22]/[C:20]1[CH2:21][C@H:15]2[C:14](=[O:43])[N:13]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:50])([CH3:51])[CH3:49])[C:12]3[CH:52]=[C:53]([O:54][CH2:55][CH2:56][CH2:57][O:58][C:59]4[C:60]([O:96][CH3:97])=[CH:61][C:62]5[C:68](=[O:69])[N:67]6[CH:70]=[C:71]([C:73]7[CH:74]=[CH:75][C:76]([N:79]8[CH2:84][CH2:83][N:82]([CH3:85])[CH2:81][CH2:80]8)=[CH:77][CH:78]=7)[CH2:72][C@H:66]6[C:65](=[O:86])[N:64]([CH2:87][O:88][CH2:89][CH2:90][Si:91]([CH3:92])([CH3:94])[CH3:93])[C:63]=5[CH:95]=4)[C:9]([O:8][CH3:7])=[CH:10][C:11]=3[C:17](=[O:18])[N:16]2[CH:19]=1

Participants

5

Reactant 2

HCID 8082PiperidineHCID 1317364549H-fluoren-9-ylmethyl N-[(E)-3-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-[4-(4-methylpiperazin-1-yl)phenyl]-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-6,11-dioxo-5-(2-trimethylsilylethoxymethyl)-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enyl]carbamate

Product 1

HCID 90409067(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-10-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dioneYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Piperidine (0.40 mL, 4.0 mmol, 14.2 eq.) was added to a stirred solution of Fmoc amine 14e (0.358 g, 0.282 mmol, 1.0 eq.) in DMF (5.0 mL). The clear solution was stirred at room temperature for 30 minutes. The reaction mixture was diluted with DCM (300 mL) and washed with water (3×300 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to afford the crude product which did not undergo further purification (0.296 g, assumed 100% yield). LC/MS (2.049 min (ES+)), m/z: 1051.2 [M+H]+.

Workup

  1. washwashed with water (3×300 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-999c5e27b22a4cc6b806eef8fe17b157
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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