Tetrahydro-2-furoic acid, (+)- → (R)-tetrahydro-furan-2-carboxylic acid (5-amino-[1,2,4]thiadiazol-3-ylmethyl)-methyl-amide

HRID 1685047Notes

Reaction equation

HRID 1685047 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([OH:8])=O.C(C1NC=CN=1)(C1NC=CN=1)=O.[CH3:21][NH:22][CH2:23][C:24]1[N:28]=[C:27]([NH2:29])[S:26][N:25]=1>CN(C=O)C.O>[NH2:29][C:27]1[S:26][N:25]=[C:24]([CH2:23][N:22]([CH3:21])[C:6]([C@H:2]2[CH2:3][CH2:4][CH2:5][O:1]2)=[O:8])[N:28]=1

Participants

6

Reactant 3

HCID 2734707Tetrahydro-2-furoic acid, (+)-HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 666631813-(N-methylaminomethyl)[1,2,4]thiadiazol-5-ylamine

Product 1

HCID 66662881(R)-tetrahydro-furan-2-carboxylic acid (5-amino-[1,2,4]thiadiazol-3-ylmethyl)-methyl-amideYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (R)-tetrahydrofuran-2-carboxylic acid (5.0 g, 43 mmol) in DMF (100 mL) was added carbonyl diimidazole (7.68 g, 47 mmol) at 0 C under N2. After 2 hours agitation at 0 C, the product obtained from Step 1 (7.0 g, 49 mmol) in DMF (20 mL) was added and the mixture was stirred at room temperature overnight. The reaction mixture was then diluted with water (800 mL), extracted with EA (10×200 mL). The combined organic layers were washed twice with brine (100 mL) and concentrated. The residue was purified by silica gel column chromatography (PE:EA=1:3) to afford (R)-tetrahydro-furan-2-carboxylic acid (5-amino-[1,2,4]thiadiazol-3-ylmethyl)-methyl-amide (5.9 g, yield: 59%) as a red syrup. LC-MS (m/z): 243.1 [M+H]+.

Workup

  1. extractionextracted with EA (10×200 mL)
  2. washThe combined organic layers were washed twice with brine (100 mL)
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography (PE:EA=1:3)

Sources & evidence

ORD record
ord-5d8ccc08e9894e92b89da4ab9c529677
Source dataset
uspto-grants-2012_04
Patent number
US08148380B2

Reaction notes

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