Sodium Chloride → HCID 86756434, compound

HRID 636009Notes

Reaction equation

HRID 636009 reaction equation
[CH:1]([N:3]([O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[C@@H:4]([CH2:13][CH2:14][CH3:15])[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:41]1[CH:45]=[CH:44][N:43]=[C:42]1[NH:46][C:47](=[O:60])[C@@H:48]([NH2:59])[CH2:49][CH2:50][CH2:51][NH:52][CH2:53][N:54]=[N:55][N+:56]([O-:58])=[O:57].[Cl-].[Na+]>CN(C=O)C>[N+:56]([N:55]=[N:54][CH2:53][NH:52][CH2:51][CH2:50][CH2:49][C@H:48]([NH:59][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:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[CH2:13][CH2:14][CH3:15])[C:47](=[O:60])[NH:46][C:42]1[S:41][CH:45]=[CH:44][N:43]=1)([O-:58])=[O:57]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 79724-Methylmorpholine2×HCID 76257Diethyl cyanophosphonateHCID 86756429HCID 86756429, compoundHCID 86756432HCID 86756432, compound

Product 1

HCID 86756434HCID 86756434, compoundYield 50.8%

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)hexanoic acid (172 mg, 0.546 mmol) in 1 mL DMF is added diethyl cyanophosphonate (98 mg, 0.60 mmol) followed by NMM (61 mg, 0.60 mmol). Stirring is continued for 30 min at 0° C. (2S)-2-Amino-5-(nitroimino-amino)methylaminopentanoic acid 1,3-thiazol-2-ylamide hydrochloride (203 mg, 0.60 mmol) is added followed by additional NMM (122 mg, 1.20 mmol). 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-diethyl 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 (5% methanol-dichloromethane) provides 166 mg of (2R,3S)-3-(formyl-2-tetrahydropyranyloxyamino)-2-(2-methyl-1-propyl)hexanoic Acid [(1S)-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-diethyl 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 (5% methanol-dichloromethane)

Sources & evidence

ORD record
ord-e99d39f7e097402f812d591cf61ceb3d
Source dataset
uspto-grants-2001_02
Patent number
US06191150B1

Reaction notes

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