Triethylamine → HCID 67228791, compound

HRID 2067861Notes

Reaction equation

HRID 2067861 reaction equation
[CH:1]([C@:4]1([C:24]([OH:26])=O)[CH2:8][CH2:7][C@@H:6]([N:9]([C@H:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[O:22][CH3:23])C(=O)C(F)(F)F)[CH2:5]1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[OH:33][C@H:34]1[C@@H:38]2[NH:39][CH2:40][C@H:35]1[N:36]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]2.CCN(CC)CC.[OH-].[Na+]>C(Cl)Cl.CN(C=O)C>[OH:33][C@H:34]1[C@@H:38]2[N:39]([C:24]([C@@:4]3([CH:1]([CH3:2])[CH3:3])[CH2:8][CH2:7][CH:6]([NH:9][CH:16]4[CH2:21][CH2:20][O:19][CH2:18][CH:17]4[O:22][CH3:23])[CH2:5]3)=[O:26])[CH2:40][C@H:35]1[N:36]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 67230504HCID 67230504, compoundHCID 86654426HCID 86654426, compound

Product 1

HCID 67228791HCID 67228791, compoundYield 250.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of the (1S,3R)-1-isopropyl-3-(2,2,2-trifluoro-N-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-yl)acetamido)cyclopentanecarboxylic acid (0.95 g, 2.5 mmol) in CH2Cl2 (5 mL) under N2 at 0° C. is added oxalyl chloride (623 mg, 4.98 mmol) and DMF (3 drops). The mixture is allowed to warm to RT and stir for 2 hr, It was then concentrated. The acid chloride was redissolved in DCM (10 ml), cooled to 0° C., and treated with (1R,4R,7S)-tert-butyl 7-hydroxy-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylate (534 mg, 0.249 mmol), followed by Et3N (0.1 ml, 0.75 mmol). The resulting mixture was warmed to RT and stirred for 2 hrs. The solution was then washed with NaHCO3 (1×5 ml), and brine (1×5 ml). The organic layer was then dried over MgSO4, filtered and concentrated, purified by chromatography (100% EtOAc-60% MeOH/EtOAc) to yield crude intermediate which was dried and concentrated. Then it was dissolved in EtOH (2 ml) and treated with NaOH (3 ml, 7.5 mmol) overnight. The reaction mixture was then purified by chromatography (100% EtOAc-100% MeOH) to yield desired product (300 mg, 25%). LC/MS (M+H)=482.3230 exp, 482.3334 obs; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.67 (dd, J=6.95, 3.66 Hz, 3H) 0.80 (dd, J=6.59, 2.93 Hz, 3H) 1.22 (br. s., 1H) 1.35-1.41 (m, 12H) 1.43-1.48 (m, 2H) 1.55-1.68 (m, 2H) 1.85-1.93 (m, 1H) 1.95-2.04 (m, 1H) 2.16-2.28 (m, 1H) 2.66-2.80 (m, 1H) 2.97-3.02 (m, 1H) 3.03-3.10 (m, 2H) 3.17-3.29 (m, 5H) 3.37-3.47 (m, 1H) 3.47-3.58 (m, 1H) 3.61-3.74 (m, 1H) 3.81-3.89 (m, 1H) 3.94-4.04 (m, 2H) 4.24 (br. s., 1H) 5.65-5.77 (m, 1H)

Workup

  1. concentrationIt was then concentrated
  2. dissolutionThe acid chloride was redissolved in DCM (10 ml)
  3. temperaturecooled to 0° C.
  4. temperatureThe resulting mixture was warmed to RT
  5. stirringstirred for 2 hrs
  6. washThe solution was then washed with NaHCO3 (1×5 ml), and brine (1×5 ml)
  7. dry with materialThe organic layer was then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by chromatography (100% EtOAc-60% MeOH/EtOAc)
  11. customto yield crude intermediate which
  12. customwas dried
  13. concentrationconcentrated
  14. dissolutionThen it was dissolved in EtOH (2 ml)
  15. customThe reaction mixture was then purified by chromatography (100% EtOAc-100% MeOH)

Sources & evidence

ORD record
ord-d8b6226756ea451586ba8fdf6951cafa
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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