Bromotrimethylsilane → ((14R,18R)-14-amino-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontyl)phosphonic acid

HRID 2407932Notes

Reaction equation

HRID 2407932 reaction equation
[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([NH:43][C:44](=[O:56])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[CH2:29][O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][P:16](=[O:23])([O:20]CC)[O:17]CC.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([NH:43][C:44](=[O:56])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[CH2:29][O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][P:16](=[O:17])([OH:20])[OH:23]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86678310diethyl((14R,18R)-14-amino-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontyl)phosphonate

Product 1

HCID 53476664((14R,18R)-14-amino-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontyl)phosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of diethyl ((14R,18R)-14-amino-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontyl)phosphonate (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was stirred at 25° C. overnight and concentrated. The crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column eluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9) to give ((14R,18R)-14-amino-18-dodecanamido-13-oxo-3,6,9,20-tetraoxa-16-thia-12-azadotriacontyl)phosphonic acid as a white solid after lyophilizing. 1H NMR (CDCl3): δ 8.84 (s, 2H), 6.54 (d, 2H), 4.20 (t, 2H), 4.07-4.11 (m, 2H), 3.49-3.70 (m, 12H), 3.31-3.36 (m, 4H), 3.00-3.02 (m, 4H), 2.72 (d, 4H), 2.15 (t, 2H), 1.43-1.55 (m, 6H), 1.16-1.22 (m, 32H), 0.80 (t, 6H). LRMS [M+H]=784.5.

Workup

  1. concentrationconcentrated
  2. customThe crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column
  3. washeluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

Sources & evidence

ORD record
ord-97d99f48c9e54616ae239b06482a3c01
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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