Methanol → HCID 86636840, compound

HRID 1943195Notes

Reaction equation

HRID 1943195 reaction equation
CS(O[CH2:6][CH:7]1[N:17]2[CH:18]3[CH:13]([N:14]=[CH:15][C:16]2=[O:19])[CH:12]=[CH:11][C:10](=[O:20])[N:9]3[CH2:8]1)(=O)=O.N1C=CC=CC=1.[NH:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:29][CH2:28]1.CO>C(#N)C.C(Cl)Cl>[O:19]=[C:16]1[CH:15]=[N:14][C:13]2=[C:18]3[N:17]1[CH:7]([CH2:6][N:27]1[CH2:28][CH2:29][CH:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:31][CH2:32]1)[CH2:8][N:9]3[C:10](=[O:20])[CH:11]=[CH:12]2

Participants

7

Reactant 4

HCID 887MethanolHCID 1049PyridineHCID 7238334-(N-Boc-amino)piperidineHCID 86642101HCID 86642101, compound

Product 1

HCID 86636840HCID 86636840, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Crude (3,8-dioxo-1,2,5a,8b-tetrahydro-3H,8H-2a,5,8a-triazaacenaphthylen-2-yl)methyl methanesulfonate (6.950 g, 23.38 mmol) was dissolved in dry acetonitrile (200 ml) and the mixture was treated with pyridine (7.55 ml, 94.0 mmol) followed by 1,1-dimethylethyl 4-piperidinylcarbamate (10.30 g, 51.4 mmol). The mixture was stirred at reflux under argon for 3 h then at 50° C. over the weekend. The mixture was then stirred at 90° C. for 2 hours, then the volatiles were removed under reduced pressure and the residue was partitioned between DCM (600 ml) and water (100 ml). The organic phase was separated and the aqueous phase was extracted with DCM (2×200 ml). The combined organic extracts were washed with water (2×100 ml) dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to give a dark tan solid; this was taken up in a minimum of 5% MeOH in DCM and chromatographed on silica, eluting with 0-10% MeOH in DCM. Appropriate fractions were combined and evaporated under reduced pressure to give the title compound as an amorphous pale tan solid (5.444 g, 56.8%).

Workup

  1. temperatureat reflux under argon for 3 h
  2. customat 50° C.
  3. stirringThe mixture was then stirred at 90° C. for 2 hours
  4. customthe volatiles were removed under reduced pressure
  5. customthe residue was partitioned between DCM (600 ml) and water (100 ml)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with DCM (2×200 ml)
  8. washThe combined organic extracts were washed with water (2×100 ml)
  9. dry with materialdried over anhydrous sodium sulphate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customto give a dark tan solid
  13. customchromatographed on silica
  14. washeluting with 0-10% MeOH in DCM
  15. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-7661664764dc4bfe99eab3589239a534
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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