Diisopropylethylamine → 6-cyclopentyl-N-[(5,6-dimethoxypyridin-2-yl)methyl]-5'-methyl-3,3'-bipyridine-5-carboxamide

HRID 1675948Notes

Reaction equation

HRID 1675948 reaction equation
[CH:1]1([C:6]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=3)=[CH:8][C:7]=2[C:19]([O-:21])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Na+].[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:33][NH2:34])=[N:29][C:30]=1[O:31][CH3:32].CCCP(O)(O)=O.C(N(C(C)C)CC)(C)C>C(#N)C.C(OCC)(=O)C>[CH:1]1([C:6]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=3)=[CH:8][C:7]=2[C:19]([NH:34][CH2:33][C:28]2[CH:27]=[CH:26][C:25]([O:24][CH3:23])=[C:30]([O:31][CH3:32])[N:29]=2)=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 204484Propylphosphonic acidHCID 574847121-(5,6-Dimethoxypyridin-2-yl)methanamineHCID 67345386Sodium 6-cyclopentyl-5'-methyl-3,3'-bipyridine-5-carboxylate

Product 1

HCID 252268156-cyclopentyl-N-[(5,6-dimethoxypyridin-2-yl)methyl]-5'-methyl-3,3'-bipyridine-5-carboxamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a suspension of sodium 6-cyclopentyl-5′-methyl-3,3′-bipyridine-5-carboxylate (6-3, 0.022 g, 0.078 mmol, 1.0 equiv) in acetonitrile (0.8 mL) was added 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 0.039 g, 0.234 mmol, 3.0 equiv), 1-propylphosphonic acid cyclic anhydride (0.149 g, 0.234 mmol, 3.0 equiv, 50 weight percent in EtOAc), and diisopropylethylamine (0.060 g, 0.47 mmol, 6.0 equiv) and the system was heated to 40° C. for 24 h. The reaction mixture was cooled and diluted with ethyl acetate (30 mL). The reaction mixture was washed with saturated sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (1×10 mL), dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (0 to 40% methanol in EtOAc, silica) followed by reverse phase chromatography (5 to 65% acetonitrile in water, 0.1% TFA buffer) to afford the desired product (6-4) as a white solid after free-basing and concentration. 1H NMR (500 MHz, CDCl3) δ 8.83 (d, J=2.5 Hz, 1H), 8.62 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 7.84 (d, J=2.0 Hz, 1H), 7.65 (s, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.90 (d, J=7.5 Hz, 1H), 6.72 (bs, 1H), 4.64 (d, J=5.0 Hz, 2H), 3.97 (s, 3H), 3.88 (s, 3H), 3.52-3.48 (m, 1H), 2.42 (s, 3H), 2.04-1.80 (m, 6H), 1.70-1.60 (m, 2H). HRMS [M+H] C25H28N4O3 calc'd 433.2234, found 433.2226.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe reaction mixture was washed with saturated sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (1×10 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified via normal phase chromatography (0 to 40% methanol in EtOAc, silica)

Sources & evidence

ORD record
ord-bab8f039142e4556b7c3c09da0cf01bb
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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