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 899852Notes

Reaction equation

HRID 899852 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-2fc720a718b24745a072d29014f77159
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Reaction notes

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