Ethylenediamine → 2-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-methyl-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1864929Notes

Reaction equation

HRID 1864929 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([N:18]([CH3:45])[C:19]3[CH:20]=[C:21]4[C:42](=[CH:43][CH:44]=3)[CH2:41][C@:23]3([C:31]5[C:26](=[N:27][CH:28]=[CH:29][CH:30]=5)[N:25](COCC[Si](C)(C)C)[C:24]3=[O:40])[CH2:22]4)=[O:17])[C:13](=[O:46])[C:12]([CH3:48])([CH3:47])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+].C(N)CN>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([N:18]([CH3:45])[C:19]3[CH:20]=[C:21]4[C:42](=[CH:43][CH:44]=3)[CH2:41][C@:23]3([C:31]5[C:26](=[N:27][CH:28]=[CH:29][CH:30]=5)[NH:25][C:24]3=[O:40])[CH2:22]4)=[O:17])[C:13](=[O:46])[C:12]([CH3:48])([CH3:47])[CH2:11][CH2:10]2)[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 669735562-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-methyl-N-((2R)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

Product 1

HCID 250199372-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-methyl-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[(6S)-6-(3,5-difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-methyl-N-((2R)-2′-oxo-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-yl]acetamide from Step B (38 mg, 0.057 mmol) in CH2Cl2 (2 mL) was added TFA (1 mL) and the resulting mixture was stirred at ambient temperature for 1 h then concentrated to dryness in vacuo. The residue was dissolved in MeOH (1 mL) and the solution was adjusted to pH 10 by addition of 1 N aqueous NaOH and ethylenediamine (5.7 mg, 0.095 mmol). After 30 min, the mixture was partitioned between H2O (30 mL) and EtOAc (40 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:CH3OH-100:0 to 95:5, to give the title compound. MS: m/z=545 (M+1). HRMS: m/z=545.2388; calculated m/z=545.2359 for C31H31F2N4O3.

Workup

  1. concentrationthen concentrated to dryness in vacuo
  2. dissolutionThe residue was dissolved in MeOH (1 mL)
  3. waitAfter 30 min
  4. customthe mixture was partitioned between H2O (30 mL) and EtOAc (40 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-735a97f0b2704b2e90a1c2afd5eff226
Source dataset
uspto-grants-2009_12
Patent number
US07625901B2

Reaction notes

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