Cesium carbonate → HCID 71737902, compound

HRID 882364Notes

Reaction equation

HRID 882364 reaction equation
Cl[CH:2]([O:4][C:5]([N:7]1[CH2:12][CH2:11][S:10](=[O:14])(=[O:13])[CH2:9][CH2:8]1)=[O:6])[CH3:3].[Cl:15][C:16]1[C:17]([F:56])=[C:18]([C@@H:22]2[C@:26]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:25]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:24][C@H:23]2[C:42]([NH:44][C:45]2[CH:53]=[CH:52][C:48]([C:49]([OH:51])=[O:50])=[CH:47][C:46]=2[O:54][CH3:55])=[O:43])[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([C@@:26]2([C:27]#[N:28])[C@H:25]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:24][C@@H:23]([C:42]([NH:44][C:45]3[CH:53]=[CH:52][C:48]([C:49]([O:51][CH:2]([O:4][C:5]([N:7]4[CH2:12][CH2:11][S:10](=[O:14])(=[O:13])[CH2:9][CH2:8]4)=[O:6])[CH3:3])=[O:50])=[CH:47][C:46]=3[O:54][CH3:55])=[O:43])[C@@H:22]2[C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[C:17]=2[F:56])=[C:30]([F:36])[CH:31]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 53358942IdasanutlinHCID 86696300HCID 86696300, compound

Product 1

HCID 71737902HCID 71737902, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (Oakwood, 1.32 g, 1 mL, 9.27 mmol) was reacted with thiomorpholine 1,1-dioxide (1.1638 g, 8.61 mmol) and pyridine (783 mg, 801 μl, 9.9 mmol) in methylene chloride (15 mL) at room temperature for 3 h to give 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-chloro-ethyl ester. A portion of 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-chloro-ethyl ester (577 mg, 1.614 mmol) 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 (150.5 mg, 0.244 mmol) in the presence of cesium carbonate (598.4 mg, 1.84 mmol) in dimethylformamide (7 mL) overnight to give 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-ethyl ester as an off-white solid (175.3 mg, 87% yield). MS (ES+) m/z calcd. for C38H41Cl2F2N4O8S: [(M+H)+]: 821, found: 821

Sources & evidence

ORD record
ord-7276a60df9b9473fa5478203a2324d7b
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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