N-(1H-benzimidazol-2-ylmethyl)-N-(5,6,7,8-tetrahydroquinolin-8-yl)-ethane-1,2-diamine → n-{2-[(1h-Benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-ethyl}-3,5-dichloro-isonicotinamide

HRID 899852ノート

反応式

HRID 899852 の反応式
[Cl:1][C:2]1[CH:10]=[N:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4](Cl)=[O:5].[NH:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[CH2:21][N:22]([CH:26]1[C:35]2[N:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:29][CH2:28][CH2:27]1)[CH2:23][CH2:24][NH2:25]>C1COCC1.ClCCl.CCN(CC)CC>[NH:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[CH2:21][N:22]([CH:26]1[C:35]2[N:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:29][CH2:28][CH2:27]1)[CH2:23][CH2:24][NH:25][C:4](=[O:5])[C:3]1[C:2]([Cl:1])=[CH:10][N:9]=[CH:8][C:7]=1[Cl:11]

参加物

6

反応物 2

HCID 10149770N-(1H-benzimidazol-2-ylmethyl)-N-(5,6,7,8-tetrahydroquinolin-8-yl)-ethane-1,2-diamineHCID 115720223,5-Dichloropyridine-4-carbon chloride

生成物 1

HCID 59694130n-{2-[(1h-Benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-ethyl}-3,5-dichloro-isonicotinamide収率 44%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒

反応条件

温度
0 °C

実験手順

To a suspension of 3,5-dichloro-isonicotinoyl chloride (0.34 mmol) in THF (3 mL) at 0° C. was added a solution of N1-(1H-benzoimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-ethane-1,2-diamine (0.100 g, 0.312 mmol) in dichloromethane (3 mL), THF (1 mL) and Et3N (0.087 mL). After stirring at 0° C. for 5 min., the mixture was warmed to room temperature and stirred for 2.5 h. The solvents were evaporated and the residue was taken into saturated aqueous NaHCO3 (30 mL). The mixture was extracted with chloroform (3×20 mL). The extracts were dried over Na2SO4 and concentrated. Purification of the crude material by column chromatography on silica gel (200:1:1 CH2Cl2—CH3OH—NH4OH) provided 55 mg (44%) of COMPOUND 152 as a pale yellow solid 1H NMR (CDCl3) δ 1.55-1.70 (m, 1H), 1.78-1.85 (m, 1H), 2.03 (m, 1H), 2.29 (m, 1H), 2.66-2.82 (m, 3H), 3.20 (d, J=13.5 Hz, 1H), 3.39 (m, 1H), 3.55 (m, 1H), 3.90 (dd, J=10.8 Hz, 5.7 Hz, 1H), 4.12 (d, J=16.7 Hz, 1H), 4.30 (d, J=16.7 Hz, 1H), 6.99 (dd, 1H, J=7.8 Hz, 4.8 Hz, 1H), 7.15-7.21 (m, 2H), 7.27 (m, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.54 (d, J=4.2 Hz, 1H), 7.63 (d, J=4.2 Hz, 1H), 8.40 (m, 1H), 8.56 (s, 2 H); 13C NMR (CDCl3) δ 21.79, 23.08, 29.32, 38.68, 48.54, 49.25, 61.63, 119.35, 122.24, 122.69, 123.19, 129.64, 133.76, 135.76, 138.70, 143.50, 144.39, 146.46, 148.03, 154.85, 157.38, 162.22; ES-MS m/z 496 (M+H). Anal. Calcd. for C25H24N6Cl2O.0.9CH2Cl2: C, 54.40; H, 4.55; N, 14.70; Cl, 23.56. Found: C, 54.64; H, 4.53; N, 14.62 Cl, 23.41.

後処理

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 2.5 h
  3. customThe solvents were evaporated
  4. extractionThe mixture was extracted with chloroform (3×20 mL)
  5. dry with materialThe extracts were dried over Na2SO4
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (200:1:1 CH2Cl2—CH3OH—NH4OH)

出典と根拠

ORDレコード
ord-2fc720a718b24745a072d29014f77159
出典データセット
uspto-grants-2008_04
特許番号
US07354934B2

反応ノート

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