N-Isopropylaniline → N'-[(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-N-isopropyl-N-phenylurea

HRID 1092569Notes

Reaction equation

HRID 1092569 reaction equation
C[Al](C)C.[CH:5]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:7])[CH3:6].[CH2:15]([N:22]1[CH2:26][C@@H:25]2[C@@H:27]([NH:30][C:31](=O)[O:32]C(C)(C)C)[CH2:28][CH2:29][C@@H:24]2[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[CH2:15]([N:22]1[CH2:26][C@@H:25]2[C@@H:27]([NH:30][C:31](=[O:32])[N:8]([CH:5]([CH3:7])[CH3:6])[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:28][CH2:29][C@@H:24]2[CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 13032N-IsopropylanilineHCID 16682925TrimethylaluminumHCID 66590514tert-butyl(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylcarbamate

Product 1

HCID 66590155N'-[(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-N-isopropyl-N-phenylurea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

2 M Trimethylaluminum in toluene (0.198 mL, 0.395 mmol) was added dropwise to N-isopropylaniline (0.068 mL, 0.474 mmol) in toluene (2 mL) at 0° C. The reaction was warmed to room temperature and stirred for 1 hour. The aluminum amide solution was then added dropwise to a solution of tert-butyl(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylcarbamate from Example 214 Step A (50 mg, 0.158 mmol) in 1 mL of toluene at 0° C. The reaction was heated at 90° C. overnight, and then the reaction was quenched with 1 mL of 5% aqueous sodium hydroxide. The separated toluene layer was applied directly to a silica gel cartridge (Analogix®, Burlington, Wis., RS-4) eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 7.40 (ddd, J=1.8, 3.2, 5.7, 3H), 7.29 (d, J=4.4, 4H), 7.24-7.18 (m, 1H), 7.14 (t, J=2.0, 1H), 7.13-7.10 (m, 1H), 4.87 (dt, J=6.8, 13.6, 1H), 3.94-3.84 (m, 1H), 3.74 (d, J=7.1, 1H), 3.60 (d, J=13.0, 1H), 3.44 (d, J=13.0, 1H), 2.53 (t, J=5.5, 2H), 2.48-2.40 (m, 1H), 2.40-2.33 (m, 1H), 2.22 (dd, J=3.7, 8.8, 1H), 2.07 (ddd, J=5.1, 9.2, 11.7, 1H), 1.95 (td, J=6.0, 12.0, 1H), 1.63-1.52 (m, 1H), 1.40-1.30 (m, 1H), 1.29-1.17 (m, 1H), 1.05 (d, J=3.2, 3H), 1.02 (d, J=3.2, 3H); MS (ESI+) m/z 378 (M+H)+.

Workup

  1. temperatureThe reaction was heated at 90° C. overnight
  2. customthe reaction was quenched with 1 mL of 5% aqueous sodium hydroxide
  3. washeluting with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-137443b3b66f44bdb296fe8e28063f4d
Source dataset
uspto-grants-2012_03
Patent number
US08129417B2

Reaction notes

Loading…