Solketal → HCID 72550679, compound

HRID 2206385Notes

Reaction equation

HRID 2206385 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.[CH3:43][C:44]1([CH3:51])[O:48][CH:47]([CH2:49]O)[CH2:46][O:45]1.[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][CH2:49][CH:47]3[CH2:46][O:45][C:44]([CH3:51])([CH3:43])[O:48]3)=[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 7528SolketalHCID 24758Sodium hydrideHCID 53358942Idasanutlin

Product 1

HCID 72550679HCID 72550679, compoundYield 27,746,624%

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 (100.8 mg, 0.164 mmol) was reacted with N,N′-carbonyldiimidazole (Aldrich, 67.8 mg, 0.406 mmol) and then a mixture of (2,2-Dimethyl-[1,3]dioxolan-4-yl)-methanol (Aldrich, 69.3 mg, 0.514 nmol) and sodium hydride (11.2 mg, 0.443 mmol) in tetrahydrofuran to give (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 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 (104.2 mg, 87% yield). MS (ES+) m/z calcd. for C37H40Cl2F2N3O6 [(M+H)+]: 730. found: 730.

Sources & evidence

ORD record
ord-3971e7d7f9a64d48addea99dee917487
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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