Triethylamine → 1H-benzimidazole-4-carboxylic acid-{4-[(3,5-dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-amide

HRID 1592479Notes

Reaction equation

HRID 1592479 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CCN(CC)CC.[NH:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[C:42]([C:43](Cl)=[O:44])[C:37]=2[N:36]=[CH:35]1>C(Cl)Cl>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:43]([C:42]2[C:37]3[N:36]=[CH:35][NH:34][C:38]=3[CH:39]=[CH:40][CH:41]=2)=[O:44])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11187147N-(3,5-dimethyl-pyridin-2-ylmethyl)-N-isoquinolin-1-ylmethyl-butane-1,4-diamineHCID 539029101H-benzoimidazole-4-carbonyl chloride

Product 1

HCID 589969441H-benzimidazole-4-carboxylic acid-{4-[(3,5-dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-amideYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N1-(3,5-dimethyl-pyridin-2-ylmethyl)-N1isoquinolin-1-ylmethyl-butane-1,4-diamine (83 mg, 0.24 mmol) in CH2Cl2 (5 mL) was added Et3N (0.13 mL, 0.96 mmol) and 1H-benzoimidazole-4-carbonyl chloride (86 mg, 0.48 mmol) and the mixture was stirred for 2 d. Then it was diluted with CH2Cl2 (20 mL) and washed with saturated NaHCO3 (3×15 mL). The organic layer was dried (MgSO4), filtered, and concentrated to afford a yellow oil. Purification by radial chromatography on silica gel (1 mm plate; using CH2Cl2/MeOH/NH4OH; 50:1:1) afforded the product as a yellow oil (34 mg, 29%). 1H NMR (CDCl3) δ 1.48-1.53 (m, 2H), 1.66 (s, 6H), 1.72 (br m, 2H), 2.03 and 2.07 (s, total 3H), 2.25 and 2.27 (s, total 3H), 2.64 (t, 2H, J=7.5 Hz), 3.30 (br m, 1H), 3.40 (br m, 1H), 3.81 and 3.87 (s, total 2H), 4.21 and 4.25 (s, total 2H), 7.37-7.42 (m, 2H), 7.55-7.57 (m, 2H), 8.04-8.07 (m, 2H), 8.13-8.17 (m, 2H), 8.38 and 8.40 (s, total 1H), 9.79 (br s, 1H). 13C NMR (CDCl3) δ 18.32, 18.43, 24.42, 26.61, 27.88, 30.10, 39.57, 53.83, 54.90, 58.23, 59.54, 115.20, 121.06, 123.26, 123.88, 126.80, 127.01, 127.27, 128.13, 130.33, 132.48, 133.33, 136.67, 139.37, 141.47, 146.47, 146.58, 154.16, 159.19. ES-MS m/z 493 [M+H]+. Anal. Calcd. for C30H32N6O.1.4CH2Cl2: C, 61.67; H, 5.74; N, 13.74. Found: C, 62.01; H, 5.79; N, 13.67.

Workup

  1. washwashed with saturated NaHCO3 (3×15 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford a yellow oil
  6. customPurification by radial chromatography on silica gel (1 mm plate; using CH2Cl2/MeOH/NH4OH; 50:1:1)

Sources & evidence

ORD record
ord-0219d344ecac4e69b4fd0a16a7fe5eab
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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