Pyridine → 1-(1-Benzyl-pyrrolidin-3-yl)-3-(3-methyl-isoquinolin-5-yl)urea

HRID 490288Notes

Reaction equation

HRID 490288 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([NH2:12])[CH:8]=[CH:7][CH:6]=2.N1C=CC=CC=1.[C:19]1([O:25]C(Cl)=O)C=CC=CC=1.C(N(CC)CC)C.[CH2:36]([N:43]1[CH2:47][CH2:46][C@@H:45]([NH2:48])[CH2:44]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>ClCCl>[CH2:36]([N:43]1[CH2:47][CH2:46][CH:45]([NH:48][C:19]([NH:12][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[C:10]=2[CH:11]=[C:2]([CH3:1])[N:3]=[CH:4]3)=[O:25])[CH2:44]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 122120553-Methylisoquinolin-5-amine

Product 1

HCID 104286221-(1-Benzyl-pyrrolidin-3-yl)-3-(3-methyl-isoquinolin-5-yl)ureaYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of (D2) (1.50 g, 10.30 mmol) and pyridine (0.91 mL,1 1.30 mmol) in dichloromethane (50 mL) was added phenylchloroformate (1.42 mL, 11.30 mmol) dropwise at 25° C. over 10 min. After 1 h, triethylamine (1.58 mL, 11.30 mmol) was added and the reaction left to stir for a further 20 min. After this period, (R)—N-benzyl-3-aminopyrrolidine (1.67 g, 10.30 mmol) was added in dichloromethane (50 mL) and the whole stirred at 25° C. for 18 h. The mixture was then diluted with dichloromethane (100 mL), washed with water (100 ml) and dried (Na2SO4). Evaporation in vacuo gave a solid, which on recrystallisation from dichloromethane/petroleum ether gave the title compound as a pale brown solid (2.56 g). 1H NMR (CDCl3)  : 2.20-2.40 (3H, m), 2.45-2.50 (1H, m), 2.63 (3H, s), 2.70-2.80 (1H, m), 2.90-3.00 (1H, m), 3.50-3.60 (2H, m), 4.25-4.35 (1H, m), 5.35 (1H, d, J=8.1 Hz), 7.15-7.20 (2H, m), 7.25-7.30 (3H, m), 7.45-7.55 (2H, m), 7.77 (2H, d, J=7.3 Hz), 9.17 (1H, s).

Workup

  1. waitthe reaction left
  2. waitAfter this period
  3. stirringthe whole stirred at 25° C. for 18 h
  4. washwashed with water (100 ml)
  5. dry with materialdried (Na2SO4)
  6. customEvaporation in vacuo
  7. customgave a solid, which
  8. customon recrystallisation from dichloromethane/petroleum ether

Sources & evidence

ORD record
ord-a0cfc8b7936c4baf93f7b5bec263223b
Source dataset
uspto-grants-2009_05
Patent number
US07528150B2

Reaction notes

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