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

HRID 251135

Reaktionsgleichung

Reaktionsgleichung von HRID 251135
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[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:37]1[CH:41]=[CH:40][N:39]=[C:38]1[NH:42][C:43](N1C=CN=C1)=[O:44]>CN(C=O)C.[Cl-].[Na+].O>[NH:37]1[CH:41]=[CH:40][N:39]=[C:38]1[NH:42][C:43]([N:14]1[CH2:15][CH2:16][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:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:21]=[CH:20][N:19]=2)[CH2:12][CH2:13]1)=[O:44]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 45120888N-(1H-Imidazol-2-yl)-1H-imidazole-1-carboxamideHCID 67271521(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-piperidin-4-yl-amine

Produkt 1

HCID 589971604-[(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amideAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a warm (70° C.), stirred, solution of (3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-piperidin-4-yl-amine (0.101 g, 0.28 mmol) and DIPEA (0.29 mL, 1.67 mmol) in DMF (3 mL) was added freshly prepared 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 column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 102 mg (75%) of COMPOUND 274 as a white solid. 1H NMR (CDCl3) δ 1.60-1.79 (m, 2H), 1.96-2.03 (m, 5H), 2.27 (s, 3H), 2.66-2.75 (m, 3H), 3.85 (s, 2H), 4.26-4.30 (m, 4H), 6.69 (s, 2H), 7.22-7.26 (m, 2H), 7.32-7.37 (m, 1H), 7.53-7.62 (m, 2H), 7.75 (d, 1H, J=8.1 Hz), 7.87 (d, 1H, J=8.7 Hz), 8.18 (s, 1H), 8.40 (d, 1H, J=6.0 Hz); 13C NMR (CDCl3) δ 18.32, 18.49, 27.57, 44.75, 54.92, 55.42, 58.07, 120.85, 126.62, 126.77, 127.23, 128.09, 130.13, 132.31, 133.26, 136.67, 139.17, 141.76, 145.51, 146.85, 154.35, 155.80, 159.42; ES-MS m/z 470 (M+H). Anal. Calcd. For C27H31N7O.1.0H2O: C, 66.51; H, 6.82; N, 20.11. Found: C, 66.34; H, 6.68; N, 19.74.

Aufarbeitung

  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 column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-3274e07dd685434197cc75ea20bf661c
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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