1,2-Dichloroethane → Mk-1064

HRID 1802360Notes

Reaction equation

HRID 1802360 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([C:20]([O-:22])=O)[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:12][CH:13]=2)[CH:5]=[N:6][CH:7]=1.[Na+].[CH3:24][O:25][C:26]1[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[C:28]([CH2:34][NH2:35])[N:27]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([C:20]([NH:35][CH2:34][C:28]3[CH:29]=[CH:30][C:31]([O:32][CH3:33])=[C:26]([O:25][CH3:24])[N:27]=3)=[O:22])[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:12][CH:13]=2)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 574847121-(5,6-Dimethoxypyridin-2-yl)methanamineHCID 67184779Sodium 5''-chloro-2,2':5',3''-terpyridine-3'-carboxylate

Product 1

HCID 44633765Mk-1064

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium 5″-chloro-2,2′:5′,3″-terpyridine-3′-carboxylate (12-4, 3.12 g, 9.35 mmol, 1.0 equiv) in dimethylformamide (47 mL) was added 1-(5,6-dimethoxy-pyridin-2-yl)methanamine (5-6, 1.65 g, 9.82 mmol, 1.05 equiv), EDC (3.58 g, 18.7 mmol, 2.0 equiv), HOAt (2.55 g, 18.7 mmol, 2.0 equiv), and diisopropylethylamine (4.83 g, 37.4 mmol, 4.0 equiv) and the system was heated to 60° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate (300 mL). The reaction mixture was washed with saturated sodium bicarbonate (2×100 mL), water (2×100 mL) and brine (1×100 mL), dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes, then 0 to 23% methanol in EtOAc, silica) to afford the desired product (12-5) as a white solid after concentration. 1H NMR (500 MHz, CDCl3) δ 8.95 (d, J=2.5 Hz, 1H), 8.80 (s, 1H), 8.66 (d, J=2.0 Hz, 1H), 8.38 (d, J=5.0 Hz, 1H), 8.26 (d, J=2.5 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.96 (bs, 1H), 7.78 (t, J=3.0 Hz, 1H), 7.47 (bs, 1H), 7.23 (dd, J=7.5, 5.5 Hz, 1H), 7.01 (d, J=7.5 Hz, 1H), 6.85 (d, J=7.5 Hz, 1H), 4.55 (d, J=5.5 Hz, 2H), 3.88 (s, 3H), 3.83 (s, 3H). HRMS [M+H] C24H20ClN5O3 calc'd 462.1327. found 462.1332.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe reaction mixture was washed with saturated sodium bicarbonate (2×100 mL), water (2×100 mL) and brine (1×100 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-2cf7862ec9ac413ba8f0727293fc136a
Source dataset
uspto-grants-2013_01
Patent number
US08349872B2

Reaction notes

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