Piperidine → (S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-methyl-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 1057075Notes

Reaction equation

HRID 1057075 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:84][CH3:85])=[CH:61][C:62]3[C:68](=[O:69])[N:67]4[CH:70]=[C:71]([CH3:73])[CH2:72][C@H:66]4[C:65](=[O:74])[N:64]([CH2:75][O:76][CH2:77][CH2:78][Si:79]([CH3:82])([CH3:81])[CH3:80])[C:63]=3[CH:83]=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]([CH3:50])([CH3:49])[CH3:51])[C:12]3[CH:52]=[C:53]([O:54][CH2:55][CH2:56][CH2:57][O:58][C:59]4[C:60]([O:84][CH3:85])=[CH:61][C:62]5[C:68](=[O:69])[N:67]6[CH:70]=[C:71]([CH3:73])[CH2:72][C@H:66]6[C:65](=[O:74])[N:64]([CH2:75][O:76][CH2:77][CH2:78][Si:79]([CH3:80])([CH3:82])[CH3:81])[C:63]=5[CH:83]=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 131736458(9H-fluoren-9-yl)methyl(E)-3-((S)-7-methoxy-8-(3-((S)-7-methoxy-2-methyl-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)-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 90407865(S)-2-((E)-3-aminoprop-1-enyl)-7-methoxy-8-(3-((S)-7-methoxy-2-methyl-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 1

HCID 6228DimethylformamideSolvent

Procedure

Piperidine (0.133 mL, 1.35 mmol, 12 eq.) was added to a stirred solution of Fmoc amine 14a (0.125 g, 0.112 mmol, 1.0 eq.) in DMF (1.8 ml). After stirring at room temperature for 30 minutes, LCMS analysis indicated consumption of starting material and the reaction mixture was diluted with DCM (200 mL) and washed with water (3×200 mL). The organic layer was dried over MgSO4, filtered and concentrated to dryness to afford the crude product which did not undergo further purification (0.100 g, assumed 100% yield). This material was used without further characterisation.

Workup

  1. customconsumption of starting material
  2. additionthe reaction mixture was diluted with DCM (200 mL)
  3. washwashed with water (3×200 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d338d3ef76234051a0c4bec681d17ffe
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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