Diisopropylethylamine → (9H-fluoren-9-yl)methyl((14R,18R)-1-(diethoxyphosphoryl)-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontan-14-yl)carbamate

HRID 2205035Notes

Reaction equation

HRID 2205035 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:23][S:24][CH2:25][C@H:26]([NH:41][C:42](=[O:54])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:20]([OH:22])=O)=[O:17])[C:11]3[C:6](=CC=CC=3)[C:5]=2C=CC=1.CN(C(ON1N=N[C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][C:64]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:79]CN(C(C)C)C(C)C.[NH2:88][CH2:89][CH2:90][O:91][CH2:92][CH2:93][O:94][CH2:95][CH2:96][O:97][CH2:98][CH2:99][P:100](=[O:107])([O:104][CH2:105][CH3:106])[O:101][CH2:102][CH3:103]>C(Cl)Cl>[CH:66]1[C:65]2[CH:14]([O:15][C:16](=[O:17])[N:18]([CH3:79])[C@@H:19]([CH2:23][S:24][CH2:25][C@H:26]([NH:41][C:42](=[O:54])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:20](=[O:22])[NH:88][CH2:89][CH2:90][O:91][CH2:92][CH2:93][O:94][CH2:95][CH2:96][O:97][CH2:98][CH2:99][P:100]([O:101][CH2:102][CH3:103])([O:104][CH2:105][CH3:106])=[O:107])[C:12]3[C:13](=[CH:1][CH:5]=[CH:6][CH:11]=3)[C:64]=2[CH:69]=[CH:68][CH:67]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67402076(R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(((R)-2-dodecanamido-3-(dodecyloxy)propyl)thio)propanoic acidHCID 86667767Diethyl 2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethylphosphonate

Product 1

HCID 86678311(9H-fluoren-9-yl)methyl((14R,18R)-1-(diethoxyphosphoryl)-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontan-14-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(((R)-2-dodecanamido-3-(dodecyloxy)propyl)thio)propanoic acid (1 eq) and HBTU (1.2 eq) in DCM (0.06 M) was added DIEA (3.5 eq), followed by diethyl(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)phosphonate (1.2 eq, from example 18, step 4). The reaction was stirred at room temperature for 2 hours. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% MeOH/DCM to give the title product as a white solid.

Workup

  1. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-233ce406dd2b475caae64ef53a1bcfec
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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