Heptane → N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide

HRID 2273620Notes

Reaction equation

HRID 2273620 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]([CH2:15][CH3:16])[CH2:5][CH2:6][O:7][C:8]1[C:9]([F:14])=[N:10][CH:11]=[CH:12][CH:13]=1.C[Al](C)C.CCCCCCC.[I:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[C:34]([C:39](OCC)=[O:40])[CH:33]=[N:32]2>ClCCl.O>[CH2:15]([N:4]([CH2:3][CH2:2][NH:1][C:39]([C:34]1[CH:33]=[N:32][C:31]2[C:36](=[CH:37][CH:38]=[C:29]([I:28])[CH:30]=2)[N:35]=1)=[O:40])[CH2:5][CH2:6][O:7][C:8]1[C:9]([F:14])=[N:10][CH:11]=[CH:12][CH:13]=1)[CH3:16]

Participants

7

Reactant 4

HCID 8900HeptaneHCID 16682925TrimethylaluminumHCID 45258965N-(2-aminoethyl)-N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amineHCID 53485588Ethyl 6-iodoquinoxaline-2-carboxylate

Product 1

HCID 44194028N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamideYield 94.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of compound 5 (55 mg, 0.24 mmol) in anhydrous dichloromethane (3 mL) was added at 0° C., under argon, a 2.0 M trimethylaluminium solution in heptane (0.12 mL, 0.24 mmol). After 10 min, a solution of compound 9 (57 mg, 0.17 mmol) in anhydrous dichloromethane (2 mL) was added and the mixture was refluxed for 6.5 h. After cooling to room temperature, water (15 mL) was added. The mixture was decanted and the aqueous layer was extrated with dichloromethane (3×20 mL). The organic layers were combined, dried on magnesium sulfate, filtered and evaporated under reduced pressure. The residue obtained was chromatographed (Al2O3, CH2Cl2/EtOH, 98/2, v/v) to give compound 10 (84 mg, 0.16 mmol) as a brown oil. Yield 94%; Rf (Al2O3, CH2Cl2/EtOH, 98/2, v/v) 0.58; IR (CCl4) ν 1453, 1468, 1522, 1684, 2750-3000 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.12 (t, 3H, J=6.8 Hz), 2.76 (q, 2H, J=6.8 Hz), 2.89 (t, 2H, J=5.7 Hz), 3.03 (t, 2H, J=5.3 Hz), 3.64 (q, 2H, J=5.7 Hz), 4.15 (t, 2H, J=5.3 Hz), 6.99 (dd, 1H, J=4.8, 7.3 Hz), 7.23 (m, 1H), 7.59 (d, 1H, J=8.8 Hz), 7.64 (m, 1H), 8.00 (d, 1H, J=8.8 Hz), 8.43 (se, 1H), 8.57 (s, 1H), 9.61 (s, 1H); ESI-MS m/z 509.9 [M+H]+.

Workup

  1. temperaturethe mixture was refluxed for 6.5 h
  2. customThe mixture was decanted
  3. customdried on magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue obtained
  7. customwas chromatographed (Al2O3, CH2Cl2/EtOH, 98/2

Sources & evidence

ORD record
ord-28503ef2244443a39561eca976157faf
Source dataset
uspto-grants-2015_09
Patent number
US09125937B2

Reaction notes

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