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

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	Chloromethyl chloroformate	HCID 62754	—
Reactant	L-Glutamic acid dibenzyl ester	HCID 3037947	—
Reactant	Idasanutlin	HCID 53358942	—
Reactant	(S)-Chloromethoxycarbonylamino-pentanedioic acid dibenzyl ester	HCID 69430907	—
Solvent	Pyridine	HCID 1049	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Dichloromethane	HCID 6344	—
Product	(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	HCID 71738207	—

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08993614B2
Source dataset	uspto-grants-2015_03
ORD ID	ord-710b833cac7d44faa7bd8081934acd0e
Source note	uspto-grants-2015_03