Sodium hydride → HCID 72550897, compound

HRID 2206386Notes

Reaction equation

HRID 2206386 reaction equation
[Cl:1][C:2]1[C:3]([F:42])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1.[OH:43][CH2:44][CH:45]([CH2:48]O)[CH2:46][OH:47].[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[C:3]([F:42])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:39]=[CH:38][C:34]([C:35]([O:37][CH2:48][CH:45]([CH2:46][OH:47])[CH2:44][OH:43])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 78432TrimethylolmethaneHCID 53358942Idasanutlin

Product 1

HCID 72550897HCID 72550897, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a manner similar to the method described in Example 7, 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 (100.2 mg, 0.163 mmol) was reacted with N,N′-carbonyldiimidazole (Aldrich, 69.5 mg, 0.416 mmol) and then, a mixture of 2-(hydroxymethyl)-1,3-propanediol (Aldrich, 91.8 mg, 0.839 mmol) and sodium hydride (41.6 mg, 1.65 mmol) in tetrahydrofuran to give chiral 3-hydroxy-2-(hydroxymethyl)propyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate as a white lyophilized solid (57.5 mg, 50% yield). MS (ES+) m/z calcd. for C35H38Cl2F2N3O6: [(M+H)+]: 704. found: 704.

Sources & evidence

ORD record
ord-91ede69b08984cf689858171c9d08b49
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

Loading…