Diisopropylethylamine → 4-{(3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-amino}-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amide

HRID 251139Notes

Reaction equation

HRID 251139 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([CH3:32])([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CCN(C(C)C)C(C)C.[NH:42]1[CH:46]=[CH:45][N:44]=[C:43]1[NH:47][C:48](N1C=CN=C1)=[O:49]>CN(C=O)C>[NH:42]1[CH:46]=[CH:45][N:44]=[C:43]1[NH:47][C:48]([N:14]1[CH2:13][CH2:12][CH:11]([N:10]([CH2:9][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=2)[CH2:17][C:18]2[C:23]([C:24]([CH3:32])([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:16][CH2:15]1)=[O:49]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 45120888N-(1H-Imidazol-2-yl)-1H-imidazole-1-carboxamideHCID 67272593HCID 67272593, compound

Product 1

HCID 589970544-{(3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-amino}-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amideYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a warm (70° C.), stirred, solution of (3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-piperidin-4-yl-amine (0.211 g, 0.49 mmol) and DIPEA (0.51 mL, 2.92 mmol) in DMF (5 mL) was added imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equivs). After 2 hours, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL) and washed with water (5×10 mL). The organic phase was dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 213 mg (76%) of COMPOUND 276 as a white solid. 1H NMR (CDCl3) δ 1.13-1.27 (m, 2H), 1.54-1.62 (m, 8H), 2.26 (s, 6H), 2.47-2.595 (m, 3H), 3.37 (s, 2H), 3.62 (s, 2H), 4.03-4.07 (m, 2H), 6.69 (s, 2H), 6.99-7.10 (m, 3H), 7.14-7.20 (m, 4H), 7.84 (d, 1H, J=7.2 Hz), 8.08 (s, 1H), 8.50 (d, 1H, J=3.6 Hz); 13C NMR (CDCl3) δ 17.31, 17.84, 27.16, 30.28, 41.87, 43.64, 53.13, 54.60, 57.03, 120.55, 125.05, 125.26, 127.82, 130.57, 132.31, 133.09, 138.09, 142.53, 144.49, 145.58, 145.90, 148.90, 154.11, 154.58, 157.80; ES-MS m/z 538 (M+1). Anal. Calcd. For C32H39N7O.0.4H2O.0.3CH2Cl2: C, 68.02; H, 7.14; N, 17.19. Found: C, 67.67; H, 7.01; N, 17.32.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
  4. washwashed with water (5×10 mL)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-602986e0690f4900be88b60eba9d1b07
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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