Allyl bromide → (1h-Benzimidazol-2-ylmethyl)-(4-diallylaminomethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

HRID 1582275Notes

Reaction equation

HRID 1582275 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][NH2:20])=[CH:15][CH:14]=1.[CH:31](N(CC)C(C)C)([CH3:33])[CH3:32].[CH2:40](Br)[CH:41]=[CH2:42]>C(Cl)Cl>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][N:20]([CH2:42][CH:41]=[CH2:40])[CH2:33][CH:31]=[CH2:32])=[CH:17][CH:18]=1)[CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 81531DiisopropylethylamineHCID 21985008N-[(1H-Benzo[d]imidazol-2-yl)methyl]-N-(4-(aminomethyl)-benzyl)-5,6,7,8-tetrahydroquinolin-8-amine

Product 1

HCID 21985148(1h-Benzimidazol-2-ylmethyl)-(4-diallylaminomethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amineYield 56.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (156 mg, 0.39 mmol) in CH2Cl2 (4 mL) was added N,N-diisopropylethylamine (65 μL, 0.37 mmol). Allyl bromide (35 μL, 0.40 mmol) was added dropwise and the resultant mixture stirred at room temperature for 3 days. The reaction mixture was diluted with CH2Cl2 (50 mL) and washed consecutively with H2O (2×5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL). The aqueous layer was extracted with CH2Cl2 (20 mL) and the combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to afford a light yellow foam (100 mg). Purification by column chromatography on silica gel (200:1:1 followed by 100:1:1—CH2Cl2:MeOH:NH4OH) followed by radial chromatography on silica gel (1000:1:1—EtOAc:MeOH:NH4OH) afforded AMD9725 (24.5 mg, 14%) as a light yellow foam. 1H NMR (CDCl3) δ1.62-1.75 (m, 1H), 1.97-2.08 (m, 2H), 2.22-2.30 (m, 1H), 2.66-2.77 (m, 1H), 2.77-2.92 (m, 1H), 3.01 (d, 4H, J=6.3 Hz), 3.48 (s, 2H), 3.74 (s, 2H), 3.99 (d, 1H, J=16.8 Hz), 4.07-4.12 (m, 1H), 4.18 (d, 1H, J=16.8 Hz), 5.09-5.17 (m, 4H), 5.83 (ddt, 2H, J=16.8, 10.2, 6.3 Hz), 7.15-7.20 (m, 5H), 7.34 (d, 2H, J=7.8 Hz), 7.41 (d, 1H, J=7.8 Hz), 7.48-7.56 (m, 1H), 7.60-7.69 (m, 1H), 8.69 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ19.69 21.65, 27.53, 46.90, 52.08, 54.63, 55.44, 58.47, 109.24, 115.61, 117.04, 119.79, 120.49, 126.67, 127.13, 132.99, 134.17, 135.45, 136.13, 136.56, 145.22, 154.64, 155.80. ES-MS m/z 478.4 (M+H). Anal. Calcd. for C31H35N5.0.5H2O: C, 76.51; H, 7.46; N, 14.39. Found: C, 76.67; H, 7.45; N, 14.18.

Workup

  1. washwashed consecutively with H2O (2×5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (20 mL)
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f4f959ad95854b07b5c74c31e61ad215
Source dataset
uspto-grants-2004_05
Patent number
US06734191B2

Reaction notes

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