Diisopropylethylamine → diethyl(12R,16R)-12-(((9H-fluoren-9-yl)methoxy)carbonylamino)-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate

HRID 2407854Notes

Reaction equation

HRID 2407854 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].Cl.[NH2:57][CH2:58][CH2:59][O:60][CH2:61][CH2:62][O:63][CH2:64][CH2:65][C:66]([P:69](=[O:76])([O:73][CH2:74][CH3:75])[O:70][CH2:71][CH3:72])([F:68])[F:67].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>[CH:35]1[C:36]2[CH:24]([CH2:23][O:22][C:21]([NH:20][C@@H:19]([CH2:18][S:17][CH2:16][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])[CH2:41][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])[C:38](=[O:39])[NH:57][CH2:58][CH2:59][O:60][CH2:61][CH2:62][O:63][CH2:64][CH2:65][C:66]([P:69](=[O:76])([O:73][CH2:74][CH3:75])[O:70][CH2:71][CH3:72])([F:68])[F:67])=[O:37])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]=2[CH:32]=[CH:33][CH:34]=1

Participants

6

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 86678263Diethyl 3-(2-(2-aminoethoxy)ethoxy)-1,1-difluoropropylphosphonate hydrochloride

Product 1

HCID 86678265diethyl(12R,16R)-12-(((9H-fluoren-9-yl)methoxy)carbonylamino)-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (0.1M) was added diethyl 3-(2-(2-aminoethoxy)ethoxy)-1,1-difluoropropylphosphonate hydrochloride (1.3 eq), DIEA (3.5 eq) and HBTU (1.2 eq). The reaction mixture was then stirred at room temperature for 2 hours. The mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 30-80% EtOAc/Hex to give the product.

Workup

  1. customThe mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  2. customto give the product

Sources & evidence

ORD record
ord-102c2e6865a4496cb5e089baea2402c9
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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