1-Hydroxybenzotriazole → 2-Amino-4-[3-(pyrimidin-2-ylcarbamoyl)-propyl]-imidazole-1-carboxylic acid tert-butyl ester

HRID 242356Notes

Reaction equation

HRID 242356 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:15]([O:19][C:20]([N:22]1[CH:26]=[C:25]([CH2:27][CH2:28][CH2:29][C:30]([OH:32])=O)[N:24]=[C:23]1[NH2:33])=[O:21])([CH3:18])([CH3:17])[CH3:16].ON1C2C=CC=CC=2N=N1.Cl.C[N:46](C)[CH2:47][CH2:48][CH2:49][N:50]=[C:51]=[N:52]CC>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH:26]=[C:25]([CH2:27][CH2:28][CH2:29][C:30](=[O:32])[NH:52][C:51]2[N:46]=[CH:47][CH:48]=[CH:49][N:50]=2)[N:24]=[C:23]1[NH2:33])=[O:21])([CH3:16])([CH3:17])[CH3:18]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 670619482-Amino-4-(3-carboxy-propyl)-imidazole-1-carboxylic acid tert-butyl esterHCID 86583742Edc hobt

Product 1

HCID 670619092-Amino-4-[3-(pyrimidin-2-ylcarbamoyl)-propyl]-imidazole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

General EDC/HOBt procedure: 2-amino-4-(3-carboxy-propyl)-imidazole-1-carboxylic acid tert-butyl ester 22 (100 mg, 0.371 mmol), 1-hydroxybenzotriazole (100 mg, 0.742 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (142 mg, 0.742 mmol) were dissolved in anhydrous DMF (3 mL). The appropriate amine coupling partner (1.48 mmol) was then added and the solution was stirred at ambient temperature until completion was evident by TLC analysis. The reaction was concentrated under reduced pressure and the residue partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was successively washed with water (3×10 mL), a 10% aqueous solution of citric acid (2×10 mL), sat. NaHCO3 (2×10 mL), and brine (10 mL) before being dried (Na2SO4) and evaporated to dryness. The crude product was purified via flash column chromatography (2-10% MeOH/CH2Cl2) to afford the target compound.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe residue partitioned between ethyl acetate (20 mL) and water (10 mL)
  3. washThe organic layer was successively washed with water (3×10 mL)
  4. dry with materiala 10% aqueous solution of citric acid (2×10 mL), sat. NaHCO3 (2×10 mL), and brine (10 mL) before being dried (Na2SO4)
  5. customevaporated to dryness
  6. customThe crude product was purified via flash column chromatography (2-10% MeOH/CH2Cl2)
  7. customto afford the target compound

Sources & evidence

ORD record
ord-9c922a017eec42029a4209d66a2e08b2
Source dataset
uspto-grants-2014_02
Patent number
US08653124B2

Reaction notes

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