Sodium Chloride → HCID 86756443, compound

HRID 636027Notes

Reaction equation

HRID 636027 reaction equation
[CH:1]([N:3]([O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1)[C@@H:4]([CH3:13])[C@@H:5]([CH2:9][CH:10]([CH3:12])[CH3:11])[C:6]([OH:8])=O)=[O:2].C(P(=O)(OCC)OCC)#N.CN1CCOCC1.Cl.[S:39]1[CH:43]=[CH:42][N:41]=[C:40]1[NH:44][C:45](=[O:59])[C@@H:46]([NH2:58])[C@H:47]([CH3:57])[CH2:48][CH2:49][NH:50][CH2:51][N:52]=[N:53][N+:54]([O-:56])=[O:55].[Cl-].[Na+]>CN(C=O)C>[CH3:57][C@H:47]([CH2:48][CH2:49][NH:50][CH2:51][N:52]=[N:53][N+:54]([O-:56])=[O:55])[C@H:46]([NH:58][C:6](=[O:8])[C@H:5]([CH2:9][CH:10]([CH3:12])[CH3:11])[C@@H:4]([N:3]([CH:1]=[O:2])[O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1)[CH3:13])[C:45](=[O:59])[NH:44][C:40]1[S:39][CH:43]=[CH:42][N:41]=1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 79724-Methylmorpholine2×HCID 76257Diethyl cyanophosphonateHCID 57218860HCID 57218860, compoundHCID 86756441HCID 86756441, compound

Product 1

HCID 86756443HCID 86756443, compoundYield 50.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a 0° C. solution of (2R,3S)-3-(formyl-2-tetrahydropyranyloxyamino)-2-(2-methyl-1-propyl)butanoic acid (34 mg, 0.12 mmol) in 1 mL anhydrous DMF is added diethyl cyanophosphonate (19 mg, 0.119 mmol) followed by NMM (12 mg). Stirring is continued for 30 min at 0° C. (2S,3R)-2-Amino-3-methyl-5-(nitroimino-amino)methylaminopentanoic acid 1,3-thiazol-2-ylamide hydrochloride (42 mg, 0.119 mmol) is added followed by additional NMM (36 mg). The mixture is heated at 40° C. for 16 h then allowed to cool to 25° C. The reaction mixture is added to half-saturated aqueous sodium chloride and extracted with 1:1 EtOAc-ether. The combined organic layers are washed with pH 4.3 phosphate buffer, 5% aqueous sodium bicarbonate, saturated aqueous sodium chloride, and dried over magnesium sulfate. Concentration and chromatography on silica gel (elution with 5% methanol in dichloromethane) provides 35 mg of (2R,3S)-3-(formyl-tetrahydropyranyloxyamino)-2-(2-methyl-1-propyl)butanoic acid [(1S,2R)-2-methyl-4-(nitroimino-amino)methylamino-1-(1,3-thiazol-2-ylcarbamoyl)-1-butyl]amide as a foam.

Workup

  1. temperatureto cool to 25° C
  2. extractionextracted with 1:1 EtOAc-ether
  3. washThe combined organic layers are washed with pH 4.3 phosphate buffer, 5% aqueous sodium bicarbonate, saturated aqueous sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. concentrationConcentration and chromatography on silica gel (elution with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-803e10b00d6c44be9ea7a8488915c4df
Source dataset
uspto-grants-2001_02
Patent number
US06191150B1

Reaction notes

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