Pyridine → HCID 68042073, compound

HRID 1943185Notes

Reaction equation

HRID 1943185 reaction equation
CS(O[CH2:6][C@H:7]1[N:17]2[C:18]3[N:9]([C:10](=[O:30])[CH2:11][N:12]([C:20]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[O:21])[C:13]=3[CH:14]=[CH:15][C:16]2=[O:19])[CH2:8]1)(=O)=O.N1C=CC=CC=1.[NH:37]1[CH2:42][CH2:41][CH:40]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH2:39][CH2:38]1>C(#N)C>[CH3:48][C:46]([O:45][C:44]([NH:43][CH:40]1[CH2:39][CH2:38][N:37]([CH2:6][C@H:7]2[N:17]3[C:18]4[N:9]([C:10](=[O:30])[CH2:11][N:12]([C:20]([O:22][CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)=[O:21])[C:13]=4[CH:14]=[CH:15][C:16]3=[O:19])[CH2:8]2)[CH2:42][CH2:41]1)=[O:50])([CH3:47])[CH3:49]

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 7238334-(N-Boc-amino)piperidine2×HCID 86642100HCID 86642100, compound

Product 1

HCID 68042073HCID 68042073, compoundYield 47.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Phenylmethyl (1S)-1-{[(methylsulfonyl)oxy]methyl}-3,8-dioxo-1,2,3,4-tetrahydro-5H,8H-2a,5,8a-triazaacenaphthylene-5-carboxylate (232 mg, 0.508 mmol) was dissolved in dry acetonitrile (10 ml) at room temperature under argon and treated with pyridine (0.049 ml, 0.610 mmol). 1,1-Dimethylethyl 4-piperidinylcarbamate (127 mg, 0.610 mmol) was then added and the reaction was heated at 70° C. overnight. Then 0.049 ml of pyridine and 127 mg of 1,1-dimethylethyl 4-piperidinylcarbamate were added to the reaction and the temperature was increased to 80° C. for 8 h and then the reaction was stirred at room temperature overnight. The solvent was evaporated and the residue partitioned between sat NaHCO3 and DCM (50/50 ml). The layers were separated and the aqueous layer was extracted with DCM again (2×50 ml). The combined organic extracts were dried (MgSO4) filtered and evaporated to afford 280 mg of crude product which was purified by silica chromatography using a 0-5% methanol/dichloromethane gradient to afford the product as a yellow gum (130 mg, 47.6%).

Workup

  1. temperaturethe temperature was increased to 80° C. for 8 h
  2. customThe solvent was evaporated
  3. customthe residue partitioned
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM again (2×50 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto afford 280 mg of crude product which
  10. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-52d84121861d4e88a4050102e027b523
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

Loading…