Ethanol → (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

HRID 1057070Notes

Reaction equation

HRID 1057070 reaction equation
[CH:1](/B(O)O)=[CH:2]\[CH3:3].[CH2:7](N(CC)CC)C.FC(F)(F)S(O[C:20]1[CH2:21][C@H:22]2[C:28](=[O:29])[N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:26]3[CH:38]=[C:39]([O:44][CH2:45][CH2:46][CH2:47][O:48][C:49]4C(OC)=C[C:52]5[C:58](=[O:59])[N:57]6[CH:60]=[C:61](/[CH:63]=[CH:64]/[CH2:65][NH:66][C:67]([O:69][CH2:70][CH:71]7[C:83]8[CH:82]=[CH:81][CH:80]=[CH:79][C:78]=8[C:77]8[C:72]7=[CH:73][CH:74]=[CH:75][CH:76]=8)=[O:68])[CH2:62][C@H:56]6[C:55](=[O:84])[N:54]([CH2:85][O:86][CH2:87][CH2:88][Si:89]([CH3:92])([CH3:91])[CH3:90])[C:53]=5[CH:93]=4)[C:40]([O:42][CH3:43])=[CH:41][C:25]=3[C:24](=[O:96])[N:23]2[CH:97]=1)(=O)=O.[CH2:100]([OH:102])[CH3:101]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][O:102][C:100]1[C:49]([O:48][CH2:47][CH2:46][CH2:45][O:44][C:39]2[C:40]([O:42][CH3:43])=[CH:41][C:25]3[C:24](=[O:96])[N:23]4[CH:97]=[C:20](/[CH:1]=[CH:2]/[CH3:3])[CH2:21][C@H:22]4[C:28](=[O:29])[N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:36])([CH3:37])[CH3:35])[C:26]=3[CH:38]=2)=[CH:93][C:53]2[N:54]([CH2:85][O:86][CH2:87][CH2:88][Si:89]([CH3:90])([CH3:92])[CH3:91])[C:55](=[O:84])[C@@H:56]3[CH2:62][C:61](/[CH:63]=[CH:64]/[CH2:65][NH:66][C:67](=[O:68])[O:69][CH2:70][CH:71]4[C:72]5[CH:73]=[CH:74][CH:75]=[CH:76][C:77]=5[C:78]5[C:83]4=[CH:82][CH:81]=[CH:80][CH:79]=5)=[CH:60][N:57]3[C:58](=[O:59])[C:52]=2[CH:101]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 6157276((1E)-prop-1-en-1-yl)boronic acidHCID 90407815[(6aS)-3-[3-[[(6aS)-8-[(E)-3-(9H-fluoren-9-ylmethoxycarbonylamino)prop-1-enyl]-2-methoxy-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] trifluoromethanesulfonate

Product 1

HCID 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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trans-1-propen-1-ylboronic acid (0.103 g, 1.20 mmol, 3.0 eq.), triethylamine (0.220 ml, 1.60 mmol, 4.0 eq.) and mono triflate 13 (0.500 g, 0.401 mmol, 1.0 eq.) were dissolved in a mixture of ethanol (10 mL), toluene (20 mL) and water (3 mL) under a nitrogen atmosphere. The reaction mixture was degassed under nitrogen for 5 minutes and tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.016 mmol, 0.04 eq.) added. The reaction mixture was stirred at 60° C. for 50 minutes, then concentrated to dryness under reduced pressure and the crude solid was purified by flash chromatography (silica gel, 50:50 acetate/hexane v/v then 66:33 ethyl acetate/hexane v/v) to afford the product as pale yellow solid. (0.35 g, 77%). LC/MS (3.910 min (ES+)), m/z: 1137.86 [M+H]+.

Workup

  1. customThe reaction mixture was degassed under nitrogen for 5 minutes
  2. concentrationconcentrated to dryness under reduced pressure
  3. customthe crude solid was purified by flash chromatography (silica gel, 50:50 acetate/hexane v/v

Sources & evidence

ORD record
ord-bf8234b25ac4497e814d1681d2b94f06
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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