Indole-3-Carboxaldehyde → (1H-benzimidazol-2-ylmethyl)-(4-{[(1H-indol-3-ylmethyl)-amino]-methyl}-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

HRID 7171

Reaction equation

HRID 7171 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=O)=[CH:2]1.[NH:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[CH2:21][N:22]([CH:32]1[C:41]2[N:40]=[CH:39][CH:38]=[CH:37][C:36]=2[CH2:35][CH2:34][CH2:33]1)[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH2:31])=[CH:26][CH:25]=1.[BH4-].[Na+]>CO>[NH:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[CH2:21][N:22]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH:31][CH2:10][C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][CH:2]=2)=[CH:26][CH:25]=1)[CH:32]1[C:41]2[N:40]=[CH:39][CH:38]=[CH:37][C:36]=2[CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 10256Indole-3-CarboxaldehydeHCID 4311764Sodium borohydrideHCID 21985008N-[(1H-Benzo[d]imidazol-2-yl)methyl]-N-(4-(aminomethyl)-benzyl)-5,6,7,8-tetrahydroquinolin-8-amine

Product 1

HCID 22018789(1H-benzimidazol-2-ylmethyl)-(4-{[(1H-indol-3-ylmethyl)-amino]-methyl}-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Using General Procedure B: 1H-Indole-3-carbaldehyde (73 mg, 0.50 mmol) and N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (200 mg, 0.50 mmol) were stirred at 40° C. in MeOH (5 mL) for 4 hours. NaBH4 (38 mg, 1.0 mmol) was added and the resultant mixture stirred at room temperature for an additional 15 minutes. Purification of the crude white foam by column chromatography on silica gel (200:1:1—EtOAc:MeOH:NH4OH) afforded AMD9673 (80 mg, 31%) as a white foam. 1H NMR (CDCl3) δ 1.59–1.75 (m, 1H), 1.81–2.09 (m, 2H), 2.16–2.30 (m, 1H), 2.64–2.76 (m, 1H), 2.76–2.91 (m, 1H), 3.69 (s, 2H), 3.78 (s, 2H), 3.92–3.98 (m, 3H), 4.04–4.09 (m, 1H), 4.15 (d, 1H, J=16.5 Hz), 7.02–7.07 (m, 2H), 7.11–7.21 (m, 6H), 7.25–7.34 (m, 3H), 7.41 (d, 1H, J=7.2 Hz), 7.54–7.57 (m, 3H), 8.68 (d, 1H, J=3.9 Hz), 8.75 (br s, 1H); 13C NMR (CDCl3) δ 21.74, 23.88, 29.60, 44.05, 48.89, 52.95, 54.06, 60.72, 111.68, 113.70, 119.08, 119.77, 121.97, 122.30, 122.66, 123.71, 127.40, 128.84, 129.07, 135.15, 136.70, 137.66, 138.60 (2 carbons), 147.27, 156.70, 157.79. ES-MS m/z 532.4 (M-C9H8N). Anal. Calcd. for C34H34N6.0.7H2O.0.2CH2Cl2: C, 73.84; H, 6.49; N, 15.11. Found: C, 73.95; H, 6.60; N, 14.81.

Workup

  1. customPurification of the crude white foam by column chromatography on silica gel (200:1:1—EtOAc:MeOH:NH4OH)
  2. customafforded AMD9673 (80 mg, 31%) as a white foam

Sources & evidence

ORD record
ord-3a5f860b3be242f1a3d8f0aaa4eee0e7
Source dataset
uspto-grants-2006_08
Patent number
US07084155B2

Linked notes

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