4-Methylmorpholine → 2-((1R)-1-{2-[(Benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-N,N-dimethyl-1,3-oxazole-4-carboxamide

HRID 2183028Notes

Reaction equation

HRID 2183028 reaction equation
[CH2:1]([O:8][NH:9][C:10](=[O:30])[CH2:11][C@H:12]([C:22]1[O:23][CH:24]=[C:25]([C:27]([OH:29])=O)[N:26]=1)[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:43][NH:44][CH3:45].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>ClCCl>[NH3:9].[CH2:1]([O:8][NH:9][C:10](=[O:30])[CH2:11][C@H:12]([C:22]1[O:23][CH:24]=[C:25]([C:27]([N:44]([CH3:45])[CH3:43])=[O:29])[N:26]=1)[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 599098342-((1R)-1-{2-[(Benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylic acid

Product 2

HCID 222AmmoniaHCID 599097552-((1R)-1-{2-[(Benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-N,N-dimethyl-1,3-oxazole-4-carboxamideYield 188.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylic acid (Preparation 65) (200 mg, 0.48 mmol) in dichloromethane (6 ml) was treated sequentially with 1-hydroxybenzotriazole hydrate (72 mg, 0.53 mmol), dimethylamine hydrochloride (79 mg, 0.96 mmol), N-methylmorpholine (160 μl, 1.45 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (111 mg, 0.58 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 4 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed sequentially with aqueous citric acid solution (10% w/v), a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was then purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia (95:5:0.5) to afford the title compound as a colourless oil (200 mg).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed sequentially with aqueous citric acid solution (10% w/v)
  4. dry with materiala saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was then purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-45858063c60d4320b59fde8cef729327
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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