2-Aminothiazole → HCID 86756440, compound

HRID 636025Notes

Reaction equation

HRID 636025 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([CH3:23])[CH2:14][CH2:15][NH:16][CH2:17][N:18]=[N:19][N+:20]([O-:22])=[O:21])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.[NH2:32][C:33]1[S:34][CH:35]=[CH:36][N:37]=1.[Cl-].[Na+]>CN(C=O)C>[S:34]1[CH:35]=[CH:36][N:37]=[C:33]1[NH:32][C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:13]([CH3:23])[CH2:14][CH2:15][NH:16][CH2:17][N:18]=[N:19][N+:20]([O-:22])=[O:21]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 5234Sodium ChlorideHCID 62365Isobutyl chloroformateHCID 86756438HCID 86756438, compound

Product 1

HCID 86756440HCID 86756440, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-23 °C

Procedure

(2S,3R)-2-tert-Butoxycarbonylamino-3-methyl-5-(nitroimino-amino)methylaminopentanoic acid (123 mg, 0.396 mmol) is dissolved in 1 mL of DMF and cooled to −23° C. TEA (51 μL, 0.37 mmol) is added followed by isobutyl chloroformate (48 μL, 0.37 mmol). After 40 min, 2-aminothiazole is added and the reaction mixture is allowed to come to 25° C. over 18 h. The reaction mixture is added to half-saturated aqueous sodium chloride and extracted with EtOAc. The combined organic layers are washed with 1N HCl, 5% sodium bicarbonate, saturated aqueous sodium chloride, and dried over magnesium sulfate. Concentration in vacuo and purification by chromatography on silica gel (elution with hexanes-EtOAc 1:5 then EtOAc) provides (2S,3R)-2-tert-butoxycarbonylamino-3-methyl-5-(nitroimino-amino)methylaminopentanoic acid 1,3-thiazol-2-ylamide as a foam (101 mg, 66%).

Workup

  1. waitto come to 25° C. over 18 h
  2. extractionextracted with EtOAc
  3. washThe combined organic layers are washed with 1N HCl, 5% sodium bicarbonate, saturated aqueous sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. concentrationConcentration
  6. customin vacuo and purification by chromatography on silica gel (
  7. washelution with hexanes-EtOAc 1:5

Sources & evidence

ORD record
ord-36fbc62b2cf54361881aa34f37b7073e
Source dataset
uspto-grants-2001_02
Patent number
US06191150B1

Reaction notes

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