4-Methylmorpholine → HCID 11478231, compound

HRID 2269346Notes

Reaction equation

HRID 2269346 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([N:16]([CH:24]=[O:25])[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH3:15])[C:11]([OH:13])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.Cl.[N:72]1[CH:77]=[CH:76][CH:75]=[C:74]([NH:78][C:79](=[O:86])[C@@H:80]([NH2:85])[C:81]([CH3:84])([CH3:83])[CH3:82])[CH:73]=1>CN(C=O)C>[CH3:82][C:81]([CH3:84])([CH3:83])[C@H:80]([NH:85][C:11](=[O:13])[C@H:10]([CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C@@H:14]([N:16]([CH:24]=[O:25])[O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[CH3:15])[C:79](=[O:86])[NH:78][C:74]1[CH:73]=[N:72][CH:77]=[CH:76][CH:75]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11245009HCID 11245009, compoundHCID 70212260HCID 70212260, compound

Product 1

HCID 11478231HCID 11478231, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (2R,3S)-2-(3-phenyl-1-propyl)-3-(formyl-2-tetrahydropyrariyloxyamino)butanoic acid (120 mg, 0.344 mmol) in DMF (1 mL) is added BOP reagent (167 mg, 0.378 mmol), HOBt (51 mg, 0.378 mmol), and NMM (174 mg, 1.72 mmol). After 30 min, (2S)-2-amino-3,3-dimethylbutanoic acid 3-pyridylamide dihydrochloride (118 mg, 0.410) is added and the resulting solution is stirred at 25° C. for 18 h. The reaction mixture is concentrated, diluted with EtOAc (20 mL) and washed sequentially with 1 M aqueous sodium carbonate and saturated aqueous sodium chloride. The organic layer is dried over magnesium sulfate, concentrated in vacuo, and purified by silica gel chromatography (elution with 2:1 EtOAc-hexane) to provide (2R,3S)-3-(formyl-2-tetrahydropyranyloxyamino)-2-(3-phenyl-1-propyl)butanoic acid [(1S)-2,2-dimethyl-1-(3-pyridylcarbamoyl)-1-propyl]amide as a solid (115 mg, 62% yield). ESI-MS m/z 529 (M+H)+.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. additiondiluted with EtOAc (20 mL)
  3. washwashed sequentially with 1 M aqueous sodium carbonate and saturated aqueous sodium chloride
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by silica gel chromatography (elution with 2:1 EtOAc-hexane)

Sources & evidence

ORD record
ord-fade9af093a64ab393021f216af59083
Source dataset
uspto-grants-2001_12
Patent number
US06329400B1

Reaction notes

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