Cesium carbonate → HCID 86696315, compound

HRID 882388Notes

Reaction equation

HRID 882388 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+].[C:49](=[O:72])([O:54][C@H:55]1[C@@H:59]2[O:60][C:61]([CH3:64])([CH3:63])[O:62][C@@H:58]2[O:57][C@H:56]1[C@@H:65]1[CH2:69][O:68][C:67]([CH3:71])([CH3:70])[O:66]1)[O:50][CH:51](Cl)[CH3:52]>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:51]([O:50][C:49]([O:54][C@@H:55]3[C@H:59]4[O:60][C:61]([CH3:64])([CH3:63])[O:62][C@H:58]4[O:57][C@@H:56]3[C@H:65]3[CH2:69][O:68][C:67]([CH3:70])([CH3:71])[O:66]3)=[O:72])[CH3:52])=[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 86696314HCID 86696314, compound

Product 1

HCID 86696315HCID 86696315, compoundYield 82.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 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, 100 mg, 162 μmol) in dry dimethyl formamide (4 mL) was added cesium carbonate (185 mg, 568 μmol). The mixture was stirred for 10 min at room temperature. The freshly made solution of 1-chloroethyl (3aS,5S,6R,6aS)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[3,2-d][1,3]dioxol-6-yl carbonate (178 mg, 487 μmol) in 4 mL of dry dimethyl formamide was added to the above mixture and stirred at room temperature overnight. It was diluted with ethyl acetate and washed with water (2×) and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give a crude, which was purified with flash chromatography (0-50% ethyl acetate in hexane over 25 min) to give an off-white solid (127 mg, 82% yield). LCMS (ES+) m/z calcd. for C46H51Cl2F2N3O12 [(M+H)+]: 946, found: 946.

Workup

  1. stirringstirred at room temperature overnight
  2. washwashed with water (2×) and brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude, which
  7. customwas purified with flash chromatography (0-50% ethyl acetate in hexane over 25 min)

Sources & evidence

ORD record
ord-b9a4ad397bf54e2aa9833d8a8c8907af
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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