Pyrazole → (αS)-α-Amino-1H-pyrazole-1-propanoic acid

HRID 1589919Notes

Reaction equation

HRID 1589919 reaction equation
S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:12][C@H:13]1[CH2:16][O:15][C:14]1=[O:17].[NH:18]1[CH:22]=[CH:21][CH:20]=[N:19]1>CN(C=O)C>[N:18]1([CH2:16][C@@H:13]([C:14]([OH:15])=[O:17])[NH2:12])[CH:22]=[CH:21][CH:20]=[N:19]1

Participants

4

Reactant 2

HCID 1048PyrazoleHCID 156005374-Methylbenzene-1-sulfonic acid--(3S)-3-aminooxetan-2-one (1/1)

Product 1

HCID 151491(αS)-α-Amino-1H-pyrazole-1-propanoic acidYield 77.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

(S)-3-Amino-2-oxetanone tosylate salt (100 mg, 0.385 mmol) was added to pyrazole (131 mg, 1.93 mmol) in distilled DMF (3.0 mL) and the mixture was stirred at 25° C. for 2.5 h. The solvent was removed in vacuo at 25° C. and the residue was dissolved in H2O (3 mL) and applied to a column of BioRad AG50-X8 (trademark) (1×10 cm, H+ form) The resin was washed with H2O (30 mL) and eluted with a gradient of aqueous NH4OH (0 to 0.25N over 70 mL, then 100 mL of 0.25N NH4OH). The product emerged chromatographically pure with 0.25N NH4OH and was lyophilized (2×) and dried in vacuo over P2O5 to yield 77% (46.2 mg) of β-(pyrazol-1-yl)-L-alanine (mp 234°-236° C. (dec)). For an improved melting point this material could be recrystallized from H2O/ EtOH: mp 241°-243° C. (lit. mp 236°-238° C. (dec), 243° C. (dec)); [α]D25 -72(±1) (c 0.54, H2O) (lit. [α]D -78° (c 3.4, H2O),-72.0° (c 1. H2O)); IR (KBr disk) 3700-2200 (m, vbr), 1617 (s), 1580 (s), 1485 (m), 1395 (m), 767 (m) cm-1 ; 1H NMR (300 MHz, D2O)δ 7.65 (d, 1H, 2 Hz, ArHH'H"), 7.61 (d, 1H, 2 Hz, ArHH'H"), 6.38 (t, 1H, 2 Hz, ArHH'H"), 4.66 (d, 2H, 5 Hz, CH2N), 4.18 (t, 1H, 5 Hz, CH); POSFAB-MS glycerol/HC1 ) 156 (MH+), 311 (M2H+); Rf 0.67 (Solvent A; characteristic blue-purple color with ninhydrin).

Workup

  1. customThe solvent was removed in vacuo at 25° C.
  2. dissolutionthe residue was dissolved in H2O (3 mL)
  3. wash(trademark) (1×10 cm, H+ form) The resin was washed with H2O (30 mL)
  4. washeluted with a gradient of aqueous NH4OH (0 to 0.25N over 70 mL
  5. dry with materialdried in vacuo over P2O5

Sources & evidence

ORD record
ord-bb14d1b2f5ea407181cf2402b211cfeb
Source dataset
uspto-grants-1993_04
Patent number
US05200526

Reaction notes

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