4-Chlorobenzenesulfonyl chloride → N-(N-(N-(N-(4-chlorobenzenesulfonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

HRID 53063Notes

Reaction equation

HRID 53063 reaction equation
[OH:1][C@H:2]1[CH2:54][C@@:53]2([CH3:55])[C@@H:13]([CH2:14][CH2:15][C@:16]2([O:56][C:57](=[O:60])[CH2:58][CH3:59])[C:17](=[O:52])[CH:18]([O:20][C:21](=[O:51])[C@H:22]([CH:48]([CH3:50])[CH3:49])[NH:23][C:24](=[O:47])[C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30](=[O:46])[C@H:31]([CH3:45])[NH:32][C:33](=[O:44])[C@H:34]([CH3:43])[NH:35]C(OC(C)(C)C)=O)[OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:63])[C:9]([C@@H:10]([CH3:61])[CH2:11]2)=[CH:8][C:7](=[O:62])[CH:6]=[CH:5]1.C(N(C(C)C)CC)(C)C.[Cl:73][C:74]1[CH:79]=[CH:78][C:77]([S:80](Cl)(=[O:82])=[O:81])=[CH:76][CH:75]=1>O1CCCC1>[OH:1][C@H:2]1[CH2:54][C@@:53]2([CH3:55])[C@@H:13]([CH2:14][CH2:15][C@:16]2([O:56][C:57](=[O:60])[CH2:58][CH3:59])[C:17](=[O:52])[CH:18]([O:20][C:21](=[O:51])[C@H:22]([CH:48]([CH3:49])[CH3:50])[NH:23][C:24](=[O:47])[C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30](=[O:46])[C@H:31]([CH3:45])[NH:32][C:33](=[O:44])[C@H:34]([CH3:43])[NH:35][S:80]([C:77]2[CH:78]=[CH:79][C:74]([Cl:73])=[CH:75][CH:76]=2)(=[O:82])=[O:81])[OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:63])[C:9]([C@@H:10]([CH3:61])[CH2:11]2)=[CH:8][C:7](=[O:62])[CH:6]=[CH:5]1

Participants

5

Reactant 3

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 131719958N-(N-(N-(N-(1,1-Dimethylethoxycarbonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

Product 1

HCID 131719960N-(N-(N-(N-(4-chlorobenzenesulfonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] esterYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

100 mg (0.11 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3) and 300 μl (1.71 mmol) of diisopropylethylamine are dissolved in 5 ml of tetrahydrofuran, mixed with 238 mg (1.13 mmol) of 4-chlorobenzenesulfonic acid chloride and stirred for 23 hours at room temperature. The residue that remains after removal of the solvent i.vac. is chromatographed. Gradient chromatography on 25 g of silica gel 60 (hexane/acetone 2:1→1:2) yields 75 mg (70%) of N-(N-(N-(N-(4-chlorobenzenesulfonyl)-L-alanyl)-L-alanyl)-L -prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester, and, after recrystallization from dichloromethane/diisopropyl ether, 47 mg (44%) of crystalline product.

Workup

  1. customafter removal of the solvent i.vac
  2. customis chromatographed

Sources & evidence

ORD record
ord-32f7ae8043d14e8ab3d08154d20b4eab
Source dataset
uspto-grants-1997_04
Patent number
US05616573

Reaction notes

Loading…