Bromotrimethylsilane → 3-(4-(2-((R)-2-amino-3-((R)-2,3-bis(dodecanoyloxy)propylthio)propanamido)ethyl)phenoxy)propylphosphonic acid

HRID 2407896Notes

Reaction equation

HRID 2407896 reaction equation
[C:1]([O:14][CH2:15][C@@H:16]([O:45][C:46](=[O:58])[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:17][S:18][CH2:19][C@H:20]([NH2:44])[C:21]([NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][P:36]([O:41]CC)([O:38]CC)=[O:37])=[CH:28][CH:27]=1)=[O:22])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C[Si](Br)(C)C>C(Cl)Cl>[NH2:44][C@@H:20]([CH2:19][S:18][CH2:17][C@H:16]([O:45][C:46](=[O:58])[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:15][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])[C:21]([NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][P:36](=[O:37])([OH:41])[OH:38])=[CH:28][CH:27]=1)=[O:22]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86678289(R)-3-((R)-2-amino-3-(4-(3-(diethoxyphosphoryl)propoxy)phenethylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

Product 1

HCID 534764323-(4-(2-((R)-2-amino-3-((R)-2,3-bis(dodecanoyloxy)propylthio)propanamido)ethyl)phenoxy)propylphosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-3-((R)-2-amino-3-(4-(3-(diethoxyphosphoryl)propoxy)phenethylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was stirred at room temperature overnight and then concentrated. The crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column eluting with a gradient of 50-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9) to give the product as a white solid. 1H NMR (DMSO-d6): δ 7.13 (d, 2H), 6.85 (d, 2H), 5.10-5.19 (m, 2H), 4.28 (dd, 1H), 4.12 (dd, 1H), 3.97 (t, 1H), 3.81-3.90 (m, 1H), 2.93 (dd, 1H), 2.70-2.86 (m, 3H), 2.64-2.70 (m, 2H), 2.31-2.35 (m, 2H), 2.24-2.31 (m, 2H), 2.14-2.21 (m, 2H), 1.82-1.93 (m, 4H), 1.57-1.70 (m, 4H), 1.41-1.57 (m, 4H), 1.07-1.38 (m, 32H), 0.85 (t, 6H). LRMS [M+H]=801.5.

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 50-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

Sources & evidence

ORD record
ord-f9723935b3ba41c79000fea30bd2d882
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

Loading…