4-Methylmorpholine → HCID 12991295, compound

HRID 1289258Notes

Reaction equation

HRID 1289258 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C@H:10]([NH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:16])[C:11]([OH:13])=O)=[CH:5][CH:4]=1)#[N:2].Cl.CN(C)[CH2:25][CH2:26][CH2:27][N:28]=[C:29]=NCC.O.ON1[C:40]2C=CC=C[C:39]=2N=N1.CN1CCOCC1>CN(C)C=O>[CH:27]1([N:28]([CH3:29])[C:11](=[O:13])[C@@H:10]([NH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:16])[CH2:9][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=2)[CH2:26][CH2:25][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53878343HCID 53878343, compound

Product 1

HCID 12991295HCID 12991295, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-3-(4-cyanophenyl)-2-(butyloxycarbonyl-amino) propionic acid (0.7 g, 2.41 mmole) in dimethylformamide (DMF, 6 ml) were added, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC, 0.7 g) and 1-hydroxybenzotriazole hydrate (HOBT, 0.4 g) at 0° C. The mixture was stirred until they are completely dissolved therein. To this reaction mixture were added the compound (0.4 g, 2.96 mmole) prepared in Preparation 1 and N-methylmorpholine(1.0 ml) and then the reaction temperature was slowly elevated to room temperature. The reaction solution was stirred for 3.5 hours. After the reaction is completed, the reaction solution was concentrated under reduced pressure to remove the volatile substances and the remaining residue was diluted with ethyl acetate, washed successively with aqueous saturated sodium hydrogen carbonate solution, dilute hydrochloric acid and brine, dried over anhydrous sodium sulfate, filtered and then concentrated. The residue was purified by column chromatography (ethyl acetate:hexane=7:3 (v/v)) to obtain the purified title compound (0.65 g, Yield: 73.0%). 1H NMR(CDCl3, ppm) δ: 7.61(m, 2H), 7.32(m, 2H), 5.48, 5.01-4.86, 4.12(3m, 3H), 2.75, 2.72, 2.62(2s, 3H), 2.90-1.20(m, 17H) Mass(FAB, m/e): 372(M+ +1)

Workup

  1. customat 0° C
  2. dissolutionare completely dissolved
  3. customwas slowly elevated to room temperature
  4. stirringThe reaction solution was stirred for 3.5 hours
  5. concentrationthe reaction solution was concentrated under reduced pressure
  6. customto remove the volatile substances
  7. additionthe remaining residue was diluted with ethyl acetate
  8. washwashed successively with aqueous saturated sodium hydrogen carbonate solution, dilute hydrochloric acid and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (ethyl acetate:hexane=7:3 (v/v))
  13. customto obtain the

Sources & evidence

ORD record
ord-b71faf07e9a14056af0c45b4ae01ede0
Source dataset
uspto-grants-1998_05
Patent number
US05747535

Reaction notes

Loading…