Cesium carbonate → (S)-dibenzyl 2-(((4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)methoxy)carbonylamino)-pentanedioate

HRID 882376Notes

Reaction equation

HRID 882376 reaction equation
ClCOC(N[C@@H](CCC(OCC1C=CC=CC=1)=O)C(OCC1C=CC=CC=1)=O)=O.[NH2:30][C@@H:31]([CH2:42][CH2:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].Cl[C:55]([O:57][CH2:58]Cl)=[O:56].[Cl:60][C:61]1[C:62]([F:101])=[C:63]([C@@H:67]2[C@:71]([C:74]3[CH:79]=[CH:78][C:77]([Cl:80])=[CH:76][C:75]=3[F:81])([C:72]#[N:73])[C@H:70]([CH2:82][C:83]([CH3:86])([CH3:85])[CH3:84])[NH:69][C@H:68]2[C:87]([NH:89][C:90]2[CH:98]=[CH:97][C:93]([C:94]([OH:96])=[O:95])=[CH:92][C:91]=2[O:99][CH3:100])=[O:88])[CH:64]=[CH:65][CH:66]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl.CN(C)C=O.N1C=CC=CC=1>[Cl:60][C:61]1[C:62]([F:101])=[C:63]([C@@H:67]2[C@:71]([C:74]3[CH:79]=[CH:78][C:77]([Cl:80])=[CH:76][C:75]=3[F:81])([C:72]#[N:73])[C@H:70]([CH2:82][C:83]([CH3:85])([CH3:86])[CH3:84])[NH:69][C@H:68]2[C:87]([NH:89][C:90]2[CH:98]=[CH:97][C:93]([C:94]([O:96][CH2:58][O:57][C:55]([NH:30][C@@H:31]([CH2:42][CH2:43][C:44]([O:46][CH2:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[O:45])[C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])=[O:56])=[O:95])=[CH:92][C:91]=2[O:99][CH3:100])=[O:88])[CH:64]=[CH:65][CH:66]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 62754Chloromethyl chloroformateHCID 3037947L-Glutamic acid dibenzyl esterHCID 53358942IdasanutlinHCID 69430907(S)-Chloromethoxycarbonylamino-pentanedioic acid dibenzyl ester

Product 1

HCID 71738207(S)-dibenzyl 2-(((4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)methoxy)carbonylamino)-pentanedioate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 23, (S)-dibenzyl 2-((chloromethoxy)-carbonylamino)pentanedioate was prepared from (S)-dibenzyl 2-aminopentanedioate and chloromethyl chloroformate in the presence of pyridine in methylene chloride. It was then reacted with chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid and cesium carbonate in dimethylformamide to give chiral (S)-dibenzyl 2-(((4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)methoxy)carbonylamino)-pentanedioate as a white solid. MS (ES+) m/z calcd. for C52H51Cl2F2N4O10 [(M+H)+]: 999, found: 999.

Sources & evidence

ORD record
ord-710b833cac7d44faa7bd8081934acd0e
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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