L-Valine → Ureidovaline

HRID 1275350Notes

Reaction equation

HRID 1275350 reaction equation
[H-].[Na+].O([C:10]([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11])C1C=CC=CC=1.N[C@H](C(O)=O)C(C)C.[CH3:28][NH:29][CH2:30][C:31]1[N:32]=[C:33]([CH:36]([CH3:38])[CH3:37])[S:34][CH:35]=1>C1COCC1>[CH3:28][N:29]([C:10]([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:15])[CH3:16])=[O:11])[CH2:30][C:31]1[N:32]=[C:33]([CH:36]([CH3:38])[CH3:37])[S:34][CH:35]=1

Participants

6

Reactant 4

HCID 6287L-ValineHCID 24758Sodium hydride2×HCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282Ureidovaline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred slurry of anhydrous 95% NaH (500 mg, 20.8 mmol) at -10° C. in 25 mL of THF was added N-phenoxycarbonyl-L-Valine (4.93 g, 20.8 mmol) followed by a 10 mL THF rinse keeping the temperature <0° C. using an ice-water bath. Following the addition of the N-protected Valine, N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.54 g, 20.8 mmol) was added at <0° C. The reaction was allowed to warm to ambient temperature. After 3 hours, 50 mL of THF was added followed by 25 mg (1 mmol) of NaH. After 16 hours at room temperature, the reaction was complete. The reaction was worked up by the procedures described in Example 1.

Workup

  1. washrinse
  2. customthe temperature <0° C.
  3. additionwas added at <0° C
  4. waitAfter 16 hours at room temperature

Sources & evidence

ORD record
ord-ba68e21f115948838c3282262b1feda5
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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