N,N-Diphenylcarbamic chloride → N-(N-(N-(N-(diphenylcarbamoyl)-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 53062

Reaction equation

HRID 53062 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.[C:73]1([N:79]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[C:80](Cl)=[O:81])[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1>ClCCl>[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][C:80](=[O:81])[N:79]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)[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 65741N,N-Diphenylcarbamic 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 131719959N-(N-(N-(N-(diphenylcarbamoyl)-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 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

150 mg (0.17 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3) and 150 μl (0.89 mmol) of diisopropylethylamine are dissolved in 6 ml of dichloromethane, mixed with 155 mg (0.37 mmol) of diphenylcarbamoyl chloride and stirred for 110 hours at room temperature. The residue that remains after removal of the solvent i.vac. is chromatographed. Gradient chromatography (Lichroprep Si60A pre-packed column, hexane→hexane/dichloromethane/methanol 30:60:10) yields 158 mg (97%) of N-(N -(N-(N-(diphenylcarbamoyl)-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, 112 mg (68%) in crystalline form from dichloromethane/diisopropyl ether.

Workup

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

Sources & evidence

ORD record
ord-afd2338aa08748c6bacca36696125a72
Source dataset
uspto-grants-1997_04
Patent number
US05616573

Linked notes

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