2,3-Dichloropyrazine → (3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine

HRID 1894929Notes

Reaction equation

HRID 1894929 reaction equation
C(/[N:14]=[CH:15]/[C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:23]2)=[CH:18][CH:17]=1)(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:33]1[C:38]([Cl:39])=[N:37][CH:36]=[CH:35][N:34]=1>C1COCC1>[Cl:39][C:38]1[C:33]([CH:15]([C:16]2[CH:25]=[C:24]3[C:19]([CH:20]=[CH:21][C:22]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)=[N:23]3)=[CH:18][CH:17]=2)[NH2:14])=[N:34][CH:35]=[CH:36][N:37]=1

Participants

4

Reactant 2

HCID 785752,3-DichloropyrazineHCID 178482705HCID 178482705, compound

Product 1

HCID 51051365(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamineYield 91.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

Benzhydryl-[1-(2-phenyl-quinolin-7-yl)-meth-(E)-ylidene]-amine (12.50 g, 31.4 mmol) was added to a 500 mL rbf fitted with a thermocouple. The flask was degassed and filled with nitrogen. THF (150 mL) was added and the solid dissolved. The mixture was cooled to −5° C. and 1.0 M of HMDS sodium salt in THF (39.2 mL) was added within 5 min. The temperature increased slightly to −3° C. The blue solution was stirred for 20 min at 0° C. and then 2,3-dichloropyrazine (5.61 g, 37.6 mmol) in THF (10 ml) was added within 3 min. The mixture was stirred for 30 min and then quenched with saturated NH4Cl/water (200 mL). EtOAc (200 mL) was added and the aqueous phase was removed. Toluene can also be used. The organic layer was washed with water (200 mL×2) and brine (200 mL). Concentrated HCl (10 mL) and water (200 mL) were added. The phases were separated and the organic layer was extracted with 0.1 M HCl (30 mL). The aqueous was washed with EtOAc (2×) and then saturated K2CO3 was used to adjust to pH 10. The aqueous solution was extracted with EtOAc (2×) and the combined organics were dried over Na2SO4, filtered, and concentrated in vacuo to a brown oil which solidified upon standing to yield the title compound as a brown solid (9.94 g, 81% yield). 1H NMR (400 MHz, CDCl3) δ ppm 2.30 (br s, 2H), 5.79 (s, 1H), 7.43-7.56 (m, 3H), 7.62 (dd, J=8.46, 1.89 Hz, 1H), 7.81 (d, J=8.34 Hz, 1H), 7.86 (d, J=8.59 Hz, 1H), 8.07 (d, J=1.01 Hz, 1H), 8.10-8.16 (m, 2H), 8.19 (d, J=8.59 Hz, 1H), 8.31 (d, J=2.27 Hz, 1H), 8.60 (d, J=2.53 Hz, 1H). MS (ES+): m/z=347.01/349.03 (100/68) [MH+].

Workup

  1. customrbf fitted with a thermocouple
  2. customThe flask was degassed
  3. additionfilled with nitrogen
  4. additionTHF (150 mL) was added
  5. dissolutionthe solid dissolved
  6. addition1.0 M of HMDS sodium salt in THF (39.2 mL) was added within 5 min
  7. temperatureThe temperature increased slightly to −3° C
  8. stirringThe mixture was stirred for 30 min
  9. customquenched with saturated NH4Cl/water (200 mL)
  10. additionEtOAc (200 mL) was added
  11. customthe aqueous phase was removed
  12. washThe organic layer was washed with water (200 mL×2) and brine (200 mL)
  13. additionConcentrated HCl (10 mL) and water (200 mL) were added
  14. customThe phases were separated
  15. extractionthe organic layer was extracted with 0.1 M HCl (30 mL)
  16. washThe aqueous was washed with EtOAc (2×)
  17. extractionThe aqueous solution was extracted with EtOAc (2×)
  18. dry with materialthe combined organics were dried over Na2SO4
  19. filtrationfiltered
  20. concentrationconcentrated in vacuo to a brown oil which

Sources & evidence

ORD record
ord-0c3a904dffde4f9b9d8f2916c5c6bf02
Source dataset
uspto-grants-2013_08
Patent number
US08513415B2

Reaction notes

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