2-(Dimethylamino)ethanol → HCID 72550678, compound

HRID 2206384Notes

Reaction equation

HRID 2206384 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][N:44]([CH3:48])[CH2:45][CH2:46]O.[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][CH2:46][CH2:45][N:44]([CH3:48])[CH3:43])=[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 79022-(Dimethylamino)ethanolHCID 24758Sodium hydrideHCID 53358942Idasanutlin

Product 1

HCID 72550678HCID 72550678, compoundYield 86.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 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, 0.164 mmol) and N,N′-carbonyldiimidazole (68.8 mg, 0.424 mmol, Aldrich) in tetrahydrofuran (5 mL) was stirred at room temperature overnight. N,N-dimethylethanolamine (44.3 mg, 0.495 mmol, Aldrich) was added to a suspension of sodium hydride (12 mg, 0.475 mmol) in tetrahydrofuran (4 mL) and stirred at room temperature for 1 h. It was then added to the above mixture and stirred at room temperature for 1 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous sodium sulfate and concentrated. the crude product was purified by flash chromatography to give chiral 2-(dimethylamino)ethyl 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 solid (97.2 mg, 86% yield). MS (ES+) m/z calcd. for C35H39Cl2F2N4O4 [(M+H)+]: 687. found: 687.

Workup

  1. stirringstirred at room temperature for 1 h
  2. additionIt was then added to the above mixture
  3. stirringstirred at room temperature for 1 h
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-5c9ae08b83284e71ab41216442d425d2
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

Loading…