Methylamine → HCID 59515538, compound

HRID 1160220Notes

Reaction equation

HRID 1160220 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:34]=[CH:33][C:6]([CH2:7][N:8]2[C:31](=[O:32])[N:11]3[N:12]=[C:13](Cl)[C:14]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=4)=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)[C:10]3=[N:9]2)=[CH:5][CH:4]=1.[CH3:37][NH2:38]>C1COCC1.O>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:31](=[O:32])[N:11]3[N:12]=[C:13]([NH:38][CH3:37])[C:14]([C:23]4[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=4)=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)[C:10]3=[N:9]2)=[CH:33][CH:34]=1

Participants

5

Reactant 2

HCID 6329MethylamineHCID 59716676HCID 59716676, compound

Product 1

HCID 59515538HCID 59515538, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(4-(trifluoromethyl)benzyl)-6-chloro-7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (50 mg, 0.091 mmol), prepared as described in Example 3, and 2.0 M methyl amine in THF (0.4 mL) was stirred at reflux for 12 h. After this time, the reaction mixture was cooled to RT and diluted with water (5 mL). The resultant solution was extracted with EtOAc (5 mL×3). The combined organic layers were washed with water (5 mL×2) followed by saturated aqueous NaCl (5 mL×2). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude product. The crude product was purified by preparative reverse phase HPLC to give the title compound, 2-(4-(trifluoromethyl)benzyl-7,8-bis(4-chlorophenyl)-6-(methylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (31.5 mg, 64%) as pale yellow solid. HPLC: 4.17 min; MS: M+H=544; 1H NMR (CDCl3), ppm: 7.55 (2H, d, J=10.0 Hz), 7.47 (2H, d, J=10.0 Hz), 7.34 (2H, d, J=10.0 Hz), 7.21 (2H, d, J=10.0 Hz), 7.09 (2H, d, J=10.0 Hz), 7.05 (2H, d, J=10.0 Hz), 5.18 (2H, s), 4.19-4-21 (1H, br), 2.95 (3H, d, J=5.0 Hz).

Workup

  1. customprepared
  2. temperatureat reflux for 12 h
  3. extractionThe resultant solution was extracted with EtOAc (5 mL×3)
  4. washThe combined organic layers were washed with water (5 mL×2)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain a crude product
  9. customThe crude product was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-2557c827801c47e3a7a5a65c553ec356
Source dataset
uspto-grants-2010_10
Patent number
US07816357B2

Reaction notes

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