Methyl iodide → Methyl 4'-[({[1-(methylamino)cyclo-propyl]carbonyl}amino)methyl]-1,1'-biphenyl-2-carboxylate

HRID 10072Notes

Reaction equation

HRID 10072 reaction equation
[NH2:1][C:2]1([C:5]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[O:6])[CH2:4][CH2:3]1.IC.[CH2:27](N(CC)CC)C>C(Cl)Cl>[CH3:27][NH:1][C:2]1([C:5]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[O:6])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 8471TriethylamineHCID 21988955Methyl 4'-({[(1-aminocyclopropyl)carbonyl]amino}methyl)-1,1'-biphenyl-2-carboxylate

Product 1

HCID 21988953Methyl 4'-[({[1-(methylamino)cyclo-propyl]carbonyl}amino)methyl]-1,1'-biphenyl-2-carboxylateYield 34.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 4′-({[(1-aminocyclopropyl)carbonyl]amino}methyl)-1,1′-biphenyl-2-carboxylate (200 mg, 0.62 mmol), prepared according to Example 1, was dissolved in 5 mL of DCM along with iodomethane (130 mg, 0.93 mmol) and triethylamine (75 mg, 0.74 mmol). After no reaction was observed at ambient temperature, the reaction mixture was heated to reflux for about two days. After the first day, additional iodomethane was added (ca. 3–5 equiv.). After two days >50% of the starting material was consumed. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel chromatography eluting with 1–10% MeOH in DCM to afford 73 mg of methyl 4′-[({[1-(methylamino)cyclo-propyl]carbonyl}amino)methyl]-1,1′-biphenyl-2-carboxylate.

Workup

  1. customwas observed at ambient temperature
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for about two days
  4. customAfter two days >50% of the starting material was consumed
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. washeluting with 1–10% MeOH in DCM

Sources & evidence

ORD record
ord-ea24b883e61146ae966eb07d2c1926f9
Source dataset
uspto-grants-2006_08
Patent number
US07091380B2

Reaction notes

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