Cesium carbonate → HCID 66665662, compound

HRID 2276525Notes

Reaction equation

HRID 2276525 reaction equation
[CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[N:5][C:6]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=2)[NH:3]1.Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1>[CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[N:5][C:6]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=2)[N:3]1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 122490Ethyl 7-bromoheptanoate2×HCID 66665333HCID 66665333, compound

Product 1

HCID 66665662HCID 66665662, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a microwave vial was added 2-methyl-6,7-diphenyl-1,2,3,4-tetrahydro-1,8-naphthyridine (step 2) (345 mg, 1.148 mmol) in NMP (1 ml) followed by ethyl 7-bromoheptanoate (0.671 ml, 3.45 mmol) and cesium carbonate (748 mg, 2.297 mmol). The resulting mixture was heated using microwave radiation at 160° C. for 2 h. Ethyl-7-bromoheptanoate (0.671 ml, 3.45 mmol) was added and heating continued for a further 2 h. The reaction mixture was partitioned between EtOAc and water and the organic portion was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-20% EtOAc in iso-hexane afforded a yellow oil which was loaded onto a Isolute™ SCX-2 cartridge and eluted with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions were concentrated in vacuo to afford racemate ethyl 7-(2-methyl-6,7-diphenyl-3,4-dihydro-1,8-naphthyridin-1(2H)-yl)heptanoate. Chiral separation of the mixture using Supercritical Fluid Chromatography afforded the individual enantiomers.

Workup

  1. temperatureThe resulting mixture was heated
  2. customat 160° C.
  3. customfor 2 h
  4. temperatureheating
  5. customThe reaction mixture was partitioned between EtOAc and water
  6. washthe organic portion was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude product by chromatography on silica eluting with 0-20% EtOAc in iso-hexane
  11. customafforded a yellow oil which
  12. washeluted with MeOH
  13. concentrationThe methanolic ammonia fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-7c264146a7ad47cb88635f5e7f254f05
Source dataset
uspto-grants-2015_09
Patent number
US09132127B2

Reaction notes

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