Ethylenediamine → Trifluoroacetic acid

HRID 1615856Notes

Reaction equation

HRID 1615856 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH2:8][C:9]3([CH2:27][C:4]=2[CH:3]=1)[C:17]1[C:12](=[N:13][CH:14]=[CH:15][CH:16]=1)[N:11](COCC[Si](C)(C)C)[C:10]3=[O:26].[CH2:28]([N:31]1[C@@:36]([C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([F:45])[CH:39]=2)([CH3:37])[CH2:35][N:34](C(OC(C)(C)C)=O)[C:33]([CH3:54])([CH3:53])[C:32]1=[O:55])[CH:29]=[CH2:30].C1(CNCC2CCCCC2)CCCCC1.[C:71]([OH:77])([C:73]([F:76])([F:75])[F:74])=[O:72].[OH-].[Na+].C(N)CN>CC(N(C)C)=O.C(Cl)Cl.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:73]([C:71]([OH:77])=[O:72])([F:76])([F:75])[F:74].[F:45][C:40]1[CH:39]=[C:38]([C@:36]2([CH3:37])[CH2:35][NH:34][C:33]([CH3:54])([CH3:53])[C:32](=[O:55])[N:31]2[CH2:28]/[CH:29]=[CH:30]/[C:2]2[N:7]=[CH:6][C:5]3[CH2:8][C:9]4([CH2:27][C:4]=3[CH:3]=2)[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10]4=[O:26])[CH:43]=[C:42]([F:44])[CH:41]=1

Participants

11

Reactant 6

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 4594378Bis(cyclohexylmethyl)amineHCID 58118667HCID 58118667, compound2×HCID 58118710HCID 58118710, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 44469125HCID 44469125, compound

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of (±)-3-chloro-1′-{[2-(trimethylsilyl)ethoxy]methyl}-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.404 g, 1.004 mmol, described in Intermediate 32) and tert-butyl (5R)-4-allyl-5-(3,5-difluorophenyl)-2,2,5-trimethyl-3-oxopiperazine-1-carboxylate (0.36 g, 0.913 mmol) in degassed DMA (5.4 mL) in a large microwave vessel was added N,N-dicyclohexylmethylamine (0.215 mL, 1.00 mmol) and the mixture was degassed for 5 min. To the resulting mixture was added bis(tri-t-butylphosphine)palladium(0) (0.154 g, 0.301 mmol) and the mixture was degassed again. The reaction mixture was heated in a microwave reactor for 20 minutes at 150° C., cooled to ambient temperature, and filtered. The filtrate was partitioned between EtOAc (100 mL) and H2O (50 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. To the crude alkene in CH2Cl2 (10 mL) was added TFA (1.05 mL, 13.6 mmol) and the resulting mixture was stirred at room temperature for 30 min. The mixture was concentrated under reduced pressure, dissolved in MeOH and 1 N sodium hydroxide (2.73 mL, 2.73 mmol) and ethylenediamine (0.323 mL, 4.79 mmol) were added. The reaction mixture was stirred for 12 h at ambient temperature, concentrated in vacuo, and purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1, to give the title compound. MS: m/z=530 (M+1), HRMS: m/z=530.2360 (M+1); calculated m/z=530.2362 (M+1) for C30H30F2N5O2.

Workup

  1. customthe mixture was degassed for 5 min
  2. customthe mixture was degassed again
  3. temperaturecooled to ambient temperature
  4. filtrationfiltered
  5. customThe filtrate was partitioned between EtOAc (100 mL) and H2O (50 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. concentrationThe mixture was concentrated under reduced pressure
  10. dissolutiondissolved in MeOH
  11. stirringThe reaction mixture was stirred for 12 h at ambient temperature
  12. concentrationconcentrated in vacuo
  13. custompurified by HPLC
  14. washeluting with a gradient of H2O

Sources & evidence

ORD record
ord-07e75ab90c9e4f9a8dfdba28f189339e
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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