Piperidine → (S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-5,11-dioxo-2-((E)-prop-1-enyl)-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 1057076Notes

Reaction equation

HRID 1057076 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:86][CH3:87])=[CH:61][C:62]3[C:68](=[O:69])[N:67]4[CH:70]=[C:71](/[CH:73]=[CH:74]/[CH3:75])[CH2:72][C@H:66]4[C:65](=[O:76])[N:64]([CH2:77][O:78][CH2:79][CH2:80][Si:81]([CH3:84])([CH3:83])[CH3:82])[C:63]=3[CH:85]=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>[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]([CH3:51])([CH3:50])[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:86][CH3:87])=[CH:61][C:62]5[C:68](=[O:69])[N:67]6[CH:70]=[C:71](/[CH:73]=[CH:74]/[CH3:75])[CH2:72][C@H:66]6[C:65](=[O:76])[N:64]([CH2:77][O:78][CH2:79][CH2:80][Si:81]([CH3:84])([CH3:83])[CH3:82])[C:63]=5[CH:85]=4)[C:9]([O:8][CH3:7])=[CH:10][C:11]=3[C:17](=[O:18])[N:16]2[CH:19]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 131736453(9H-fluoren-9-yl)methyl(E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-5,11-dioxo-2-((E)-prop-1-enyl)-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)propoxy)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)allylcarbamate

Product 1

HCID 90407563(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-5,11-dioxo-2-((E)-prop-1-enyl)-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 1

HCID 6228DimethylformamideSolvent

Procedure

Piperidine (0.40 mL, 4.0 mmol, 12 eq.) was added to a stirred solution of Fmoc amine 14c (0.380 g, 0.334 mmol, 1.0 eq.) in DMF (5.0 mL). After stirring at room temperature for 20 minutes, LCMS analysis indicated consumption of starting material and 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 to dryness under reduced pressure to afford the crude product which did not undergo further purification (0.306 g, assumed 100% yield).

Workup

  1. customconsumption of starting material
  2. additionthe reaction mixture was diluted with DCM (300 mL)
  3. washwashed with water (3×300 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-d52da9ecd48a4450b8d1e1fb692a70ac
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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