4-Pyridinecarboxaldehyde → (1H-Benzimidazol-2-ylmethyl)-pyridin-4-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

HRID 1582298

Reaction equation

HRID 1582298 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][NH:18][CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=O)(C)(C)C.[N:29]1[CH:34]=[CH:33][C:32]([CH:35]=O)=[CH:31][CH:30]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][N:18]([CH2:35][C:32]1[CH:33]=[CH:34][N:29]=[CH:30][CH:31]=1)[CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 133894-PyridinecarboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 21985099(1H-Benzimidazol-2-ylmethyl)-pyridin-4-ylmethyl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amineYield 70.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Following General Procedure B: To a solution of (1-tert-butoxycarbonyl-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amine (120 mg, 0.32 mmol) and 4-pyridinecarboxaldehyde (30 μL, 0.32 mmol) in CH2Cl2 (5 mL) was added sodium triacetoxyborohydride (136 mg, 0.64 mmol) and the reaction stirred for 18 h. The resulting crude material was taken up in neat TFA (1 mL) and stirred 3 h. Saturated aqueous sodium bicarbonate (5 mL) was added, and the resulting mixture was extracted with CH2Cl2 (3×10 mL) then the combined organic extracts were dried (MgSO4), and concentrated in vacuo. Purification of the crude material by radial chromatography (1 mm plate, 50:1:1 CH2Cl2-MeOH-NH4OH) afforded the title compound (83 mg, 70%) as a white solid. 1H NMR (CDCl3) δ1.68-1.72 (m, 1H), 1.97-2.06 (m, 2H), 2.26-2.30 (m, 1H), 2.74-2.77 (m, 1H), 2.80-2.86 (m, 1H), 3.77 (s, 2H), 3.92 (d, 1H, J=16 Hz), 4.09 (dd, 1H, J=9, 7 Hz), 4.17 (d, 1H, J=16 Hz), 7.18-7.22 (m, 3H), 7.36 (d, 2H, J=6 Hz), 7.44 (dd, 1H, J=7.1 Hz), 7.52 (br d, 1H, J=7 Hz), 7.66 (br d, 1H, J=7 Hz), 8.46 (dd, 2H, J=5, 2 Hz), 8.70 (dd, 1H, J=5, 1 Hz); 13C NMR (CDCl3) δ21.2, 23.8, 29.0, 49.1, 53.0, 60.5, 110.9, 118.8, 121.4, 121.9, 122.5, 123.3, 133.7, 134.7, 137.4, 144.2, 146.9, 148.7, 149.8, 155.4, 156.9. ES-MS m/z 370 (M+H). Anal. Calcd. for C23H23N5.0.2H2O.0.2CH2Cl2: C, 71.44; H, 6.15; N, 17.95. Found: C, 71.63; H, 6.30; N, 17.77.

Workup

  1. stirringstirred 3 h
  2. extractionthe resulting mixture was extracted with CH2Cl2 (3×10 mL)
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude material by radial chromatography (1 mm plate, 50:1:1 CH2Cl2-MeOH-NH4OH)

Sources & evidence

ORD record
ord-56869118e1b94eea986ba27990d56e65
Source dataset
uspto-grants-2004_05
Patent number
US06734191B2

Linked notes

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