Diisopropylethylamine → 1-{4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-3-(1H-imidazol-2-yl)-1-methyl-urea

HRID 251012

反応式

HRID 251012 の反応式
[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)[CH2:11][CH2:12]CCNC)=[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]([N:45]1[CH:49]=[CH:48]N=[CH:46]1)=[O:44]>CN(C=O)C>[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)[CH2:11][CH2:12][CH2:48][CH2:49][N:45]([CH3:46])[C:43]([NH:42][C:38]2[NH:37][CH:41]=[CH:40][N:39]=2)=[O:44])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 11462607N-(3,5-Dimethyl-pyridin-2-ylmethyl)-N-isoquinolin-1-ylmethyl-N'-methyl-butane-1,4-diamineHCID 45120888N-(1H-Imidazol-2-yl)-1H-imidazole-1-carboxamide

生成物 1

HCID 589969931-{4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-butyl}-3-(1H-imidazol-2-yl)-1-methyl-urea収率 86%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

To a warm (70° C.), stirred, solution of N-(3,5-Dimethyl-pyridin-2-ylmethyl)-N-isoquinolin-1-ylmethyl-N′-methyl-butane-1,4-diamine (0.204 g, 0.56 mmol) and DIPEA (0.59 mL, 3.39 mmol) in DMF (5 mL) was added freshly prepared imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equivs). After 1.5 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 234 mg (86%) of COMPOUND 156 as a white solid. 1H NMR (CDCl3) δ 1.26-1.34 (m, 2H), 1.42-1.48 (m, 2H), 2.09 (s, 3H), 2.28 (s, 3H), 2.58 (t, 2H, J=7.5 Hz), 2.74 (s, 3H), 3.10 (t, 2H, J=7.5 Hz), 3.80 (s, 2H), 4.17 (s, 2H), 6.68 (s, 2H), 7.24-7.26 (m, 1H), 7.35-7.40 (m, 1H), 7.52-7.60 (m, 2H), 7.73 (d, 1H, J=8.1 Hz), 7.97 (d, 1H, J=8.7 Hz), 8.22 (s, 1H), 8.41 (d, 1H, J=5.7 Hz); 13C NMR (CDCl3) δ 18.33, 18.40, 23.93, 25.82, 34.90, 48.89, 54.57, 59.86, 59.96, 120.82, 126.71, 126.92, 127.20, 128.12, 130.13, 132.27, 133.15, 136.62, 139.08, 141.76, 145.16, 146.87, 154.33, 156.14, 159.39; ES-MS m/z 472 (M+1). Anal. Calcd. For C27H33N7O.0.5H2O: C, 67.48; H, 7.13; N, 20.40. Found: C, 67.57; H, 7.08; N, 20.52.

後処理

  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)

出典と根拠

ORDレコード
ord-5046f32a32c24187b62efb49c8bf1c77
出典データセット
uspto-grants-2011_01
特許番号
US07863293B2

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