Ammonia → HCID 59909844, compound

HRID 1279865Notes

Reaction equation

HRID 1279865 reaction equation
[CH2:1]([O:8][NH:9][C:10](=[O:32])[CH2:11][C@H:12]([C:22]1[O:23][C:24]([CH3:31])=[C:25]([C:27]([O:29]C)=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.O[N:35]1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.N>ClCCl>[NH3:9].[CH2:1]([O:8][NH:9][C:10](=[O:32])[CH2:11][C@H:12]([C:22]1[O:23][C:24]([CH3:31])=[C:25]([C:27]([NH2:35])=[O:29])[N:26]=1)[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59909776HCID 59909776, compound

Product 2

HCID 222AmmoniaHCID 59909844HCID 59909844, compoundYield 139.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}4-cyclohexylbutyl)-5-methyl-1,3-oxazole4-carboxylate (Preparation 72) (200 mg, 0.47 mmol) in dichloromethane (10 ml) was treated sequentially with 1-hydroxybenzotriazole hydrate (63 mg, 0.47 mmol), N-methylmorpholine (77 μl, 0.70 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (134 mg, 0.70 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 10 minutes. Concentrated ammonia solution (0.88, 50 μl, 1.00 mmol) was then added and the mixture was stirred for 17 hours. The mixture was diluted with dichloromethane and washed sequentially with water, 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 (97:3:0.3) to afford the title compound as a white solid (140 mg).

Workup

  1. stirringthe mixture was stirred for 17 hours
  2. washwashed sequentially with water
  3. dry with materiala saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe residue was then purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-e5436455f41d4be3a40170febfeaa43c
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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