Diisopropylethylamine → (R)-3-((R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-(3-(diethoxyphosphoryl)propoxy)phenethylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

HRID 2407894Notes

Reaction equation

HRID 2407894 reaction equation
[C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@@H:19]([C:38](O)=[O:39])[NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:56][CH2:57][CH2:58][C:59]1[CH:76]=[CH:75][C:62]([O:63][CH2:64][CH2:65][CH2:66][P:67](=[O:74])([O:71][CH2:72][CH3:73])[O:68][CH2:69][CH3:70])=[CH:61][CH:60]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(OCC)(=O)C>[C:43]([O:42][CH2:41][C@@H:15]([O:14][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:16][S:17][CH2:18][C@H:19]([NH:20][C:21]([O:22][CH2:23][CH:24]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:30]=2[C:31]2[C:36]1=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:37])[C:38]([NH:56][CH2:57][CH2:58][C:59]1[CH:60]=[CH:61][C:62]([O:63][CH2:64][CH2:65][CH2:66][P:67]([O:68][CH2:69][CH3:70])([O:71][CH2:72][CH3:73])=[O:74])=[CH:75][CH:76]=1)=[O:39])(=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67414703(5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acidHCID 86678288Diethyl 3-(4-(2-aminoethyl)phenoxy)propylphosphonate

Product 1

HCID 86678290(R)-3-((R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-(3-(diethoxyphosphoryl)propoxy)phenethylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acid (6, 1 eq) in DCM (0.1 M) was added diethyl 3-(4-(2-aminoethyl)phenoxy)propylphosphonate (1.1 eq), DIEA (2.5 equiv) and HBTU (1.1 eq). The reaction mixture was then stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate, and washed with 5% citric acid three times, saturated NaHCO3 solution twice, water and brine. The organic layer was dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 60-100% EtOAc/Hex to give the product.

Workup

  1. washwashed with 5% citric acid three times, saturated NaHCO3 solution twice
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated en vaccuo
  4. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  5. customto give the product

Sources & evidence

ORD record
ord-ec140881a0044cd185f9e9f876e63a50
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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