Cesium carbonate → HCID 71738702, compound

HRID 882348Notes

Reaction equation

HRID 882348 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.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH:50]([O:52][C:53](=[O:60])[N:54]([CH2:58][CH3:59])[CH:55]([CH3:57])[CH3:56])[CH3:51]>CN(C)C=O.C(OCC)(=O)C>[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][CH:50]([O:52][C:53](=[O:60])[N:54]([CH2:58][CH3:59])[CH:55]([CH3:56])[CH3:57])[CH3:51])=[O:36])=[CH:33][C:32]=2[O:40][CH3:41])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 53358942IdasanutlinHCID 866962961-Chloroethyl ethylisopropylcarbamate

Product 1

HCID 71738702HCID 71738702, compoundYield 54.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution 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 (prepared as described in US20100152190A1, 150 mg, 0.243 mmol) in dimethylformamide (6 mL) was added cesium carbonate (243 mg, 0.746 mmol). After stirring for a few minutes, a solution of the above freshly made ethyl-isopropyl-carbamic acid 1-chloro-ethyl ester (190 mg, 0.491 mmol) in dry dimethylformamide (1 mL) was added and the reaction mixture was allowed to stir at room temperature overnight. This reaction mixture was diluted with ethyl acetate and washed with water, brine and concentrated to dryness. The crude material was purified by chromatography (hexane/ethyl acetate, 90/10 to 10/90) to give 1-(ethyl(isopropyl)-carbamoyloxy)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 (102 mg, 54% yield). LCMS (ES+) m/z calcd. for C39H45Cl2F2N4O6 [(M+H)−]: 773, found: 773.

Workup

  1. stirringto stir at room temperature overnight
  2. washwashed with water, brine
  3. concentrationconcentrated to dryness
  4. customThe crude material was purified by chromatography (hexane/ethyl acetate, 90/10 to 10/90)

Sources & evidence

ORD record
ord-4bfbd3cfe04545d78f5212d0f7f8ad84
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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