Diisopropylethylamine → 4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amide

HRID 1592625Notes

Reaction equation

HRID 1592625 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:11]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CCN(C(C)C)C(C)C.[NH:36]1[CH:40]=[CH:39][N:38]=[C:37]1[NH:41][C:42](N1C=CN=C1)=[O:43]>CN(C=O)C.[Cl-].[Na+].O>[NH:36]1[CH:40]=[CH:39][N:38]=[C:37]1[NH:41][C:42]([N:24]1[CH2:23][CH2:22][CH:21]([N:10]([CH2:9][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=2)[CH:11]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:14][CH2:13][CH2:12]2)[CH2:26][CH2:25]1)=[O:43]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 45120888N-(1H-Imidazol-2-yl)-1H-imidazole-1-carboxamideHCID 67272658(3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

Product 1

HCID 589971504-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amideYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

To a warm (70° C.), stirred, solution of (3,5-dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (0.43 g, 0.41 mmol) and DIPEA (0.43 mL, 2.47 mmol) in DMF (4 mL) was added imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equivs). After 1 hour, the mixture was cooled to room temperature, diluted with brine (5 mL) and extracted with CH2Cl2 (4×10 mL). The combined organic extracts were washed with water (5×10 mL), dried (Na2SO4) and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 25:1:1 CH2Cl2-MeOH—NH4OH) provided 70 mg (31%) of COMPOUND 368 as a white solid. 1H NMR (CDCl3) δ 1.52-2.06 (m, 8H), 2.21 (s, 3H), 2.38 (s, 3H), 2.56-2.79 (m, 5H), 3.91-4.21 (m, 5H), 6.68 (s, 2H), 6.96 (dd, 1H, J=7.5, 4.5 Hz), 7.12 (s, 1H), 7.23-7.27 (m, 1H), 8.09 (s, 1H), 8.41 (d, 1H, J=3.6 Hz); 13C NMR (CDCl3) δ 18.27, 19.02, 22.26, 29.28, 29.81, 30.93, 31.98, 44.84, 44.98, 53.77, 58.48, 60.37, 112.13, 121.44, 123.44, 131.64, 133.40, 132.32, 136.38, 139.06, 145.49, 146.39, 147.30, 155.71, 155.77, 159.01; ES-MS m/z 460 (M+H). Anal. Calcd. For C26H33N7O.1.0CH2Cl2: C, 58.86; H, 6.42; N, 17.73. Found: C, 59.01; H, 6.32; N, 17.68.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. extractionextracted with CH2Cl2 (4×10 mL)
  3. washThe combined organic extracts were washed with water (5×10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 25:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-384bc52fb0ac4bd784402dd63d3b5cc2
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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