Benzylamine → N,N'-Dicyclohexylurea

HRID 840282Notes

Reaction equation

HRID 840282 reaction equation
C1C=CC2N([OH:10])N=NC=2C=1.C(N)C1C=CC=CC=1.[CH2:19]1[CH2:24][CH2:23][CH:22]([N:25]=[C:26]=[N:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:21][CH2:20]1>C(#N)C>[C:26]([NH:25][CH:22]1[CH2:21][CH2:20][CH2:19][CH2:24][CH2:23]1)([NH:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:10]

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-Hydroxybenzotriazole

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Fmoc-arginine(PMC)-OH AA3 (3.83 g, 5.0 mm) and HOBT (0.76 g, 5.0 mm) were combined in acetonitrile (100 mL), benzylamine (0.54 g, 5.0 mm) was added in dropwise at about rt, followed by DCC (2.06 g, 10.0 mm) and stirred for about 16 h. The solid was filtered and the filtrate was evaporated in vacuo to an oil, which was dissolved in ethyl acetate (100 mL) and washed with saturated NaHCO3 (2×), brine (2×), dried (Na2SO4) and was evaporated in vacuo to a solid, which was triturated with hexane (2×) to give a solid (impure with dicyclohexylurea). A portion of the solid (0.52 g, 0.70 mm) was dissolved in ACN (30 mL), diethyl amine (1.5 mL) was added and the reaction was stirred at about rt for about 1 h. The solution was evaporated in vacuo to a solid, which was triturated with hexane (3×) and evaporated in vacuo to a solid. The resulting solid was combined in ACN (20 mL) with bromoacetic acid (0.10 g, 0.70 mm) and HOBT (0.11 g, 0.7 mm). DCC (0.29 g, 1.4 mm) was added to the solution and the reaction was stirred at about rt for about 2 h. The solid was filtered and discarded and the filtrate was evaporated in vacuo to an oil. The oil was dissolved in ethyl acetate (25 mL) and washed with saturated NaHCO3 (3×), brine (2×), dried (Na2SO4) and evaporated in vacuo to an oil. The resulting oil was dissolved in DCM (10 mL), 4-fluorobenzylamine (88 mg, 0.70 mm) and triethylamine (101 mg, 1.0 mm) were added and the reaction stirred at about rt for about 24 h. The solution was evaporated in vacuo to an oil, which was purified by column chromatography to afford amine AA4.

Workup

  1. filtrationThe solid was filtered
  2. customthe filtrate was evaporated in vacuo to an oil, which
  3. dissolutionwas dissolved in ethyl acetate (100 mL)
  4. washwashed with saturated NaHCO3 (2×), brine (2×)
  5. dry with materialdried (Na2SO4)
  6. customwas evaporated in vacuo to a solid, which
  7. customwas triturated with hexane (2×)

Sources & evidence

ORD record
ord-a271409cf9f74dd5ac366000c4b347a0
Source dataset
uspto-grants-2002_04
Patent number
US06365617B1

Reaction notes

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