Allyl bromide → (4-allylaminomethyl-benzyl)-(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

HRID 8938Notes

Reaction equation

HRID 8938 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].C(Br)C=C>C(Cl)Cl>[CH2:33]([NH:20][CH2:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:11]([CH2:10][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH:21]2[C:30]3[N:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH2:24][CH2:23][CH2:22]2)=[CH:18][CH:17]=1)[CH:31]=[CH2:32]

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 21985145(4-allylaminomethyl-benzyl)-(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (200 mg, 0.39 mmol) in CH2Cl2 (˜0.4 mL) was added N,N-diisopropylethylamine (90 μL, 0.52 mmol). Allyl bromide (35 μL, 0.40 mmol) was dissolved in CH2Cl2 (˜9.6 mL) and added to the amine mixture at a rate of 5.5 mL/hour. The resultant mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with CH2Cl2 (50 mL) and washed consecutively with H2O (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. Purification by column chromatography on silica gel (200:1:1 followed by 100:1:1—EtOAc:MeOH:NH4OH) followed by radial chromatography on silica gel (250:1:1—EtOAc:MeOH:NH4OH) afforded AMD9725 (36 mg, 21%) as a light yellow foam. 1H NMR (CDCl3) δ 1.56–1.75 (m, 1H), 1.97–2.08 (m, 2H), 2.24–2.31 (m, 1H), 2.65–2.77 (m, 1H), 2.77–2.91 (m, 1H), 3.21 (d, 2H, J=5.7 Hz), 3.69 (s, 2H), 3.73 (s, 2H), 3.97 (d, 1H, J=16.8 Hz), 4.04–4.16 (m, 1H), 4.17 (d, 1H, J=16.8 Hz), 5.07 (d, 1H, J=9.9 Hz), 5.15 (dd, 1H, J=17.1, 1.2 Hz), 5.88 (ddt, 1H, J=17.1, 10.5, 6.0 Hz), 7.10–7.19 (m, 5H), 7.35 (d, 2H, J=7.8 Hz), 7.42 (d, 1H, J=7.5 Hz), 7.45–7.57 (m, 1H), 7.58–7.68 (m, 1H), 8.69 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 20.83, 22.89, 28.67, 47.95, 51.11, 52.33, 53.17, 59.68, 110.37, 115.39, 118.11, 120.91, 121.66, 127.59, 128.07, 134.13, 136.17, 136.60, 137.48, 138.56, 146.38, 155.80, 156.94. ES-MS m/z 438.3 (M+H). Anal. Calcd. for C28H31N5.0.8H2O: C, 74.40; H, 7.27; N, 15.49. Found: C, 74.36; H, 7.25; N, 15.31.

Workup

  1. washwashed consecutively with H2O (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
  5. customPurification by column chromatography on silica gel (200:1:1 followed by 100:1:1—EtOAc:MeOH:NH4OH)
  6. customafforded AMD9725 (36 mg, 21%) as a light yellow foam

Sources & evidence

ORD record
ord-73213d6191a84b5a8196e33486f8db14
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Reaction notes

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