Water → HCID 66679419, compound

HRID 1627435Notes

Reaction equation

HRID 1627435 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH:3]=1.O.[NH2:23][NH2:24].[F:25][C:26]([F:37])([F:36])[O:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1.O>O1CCOCC1.C(O)C.C(O)(=O)C.C(Cl)(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:4]2[CH:3]=[C:2]([NH:23][N:24]=[CH:32][C:31]3[CH:34]=[CH:35][C:28]([O:27][C:26]([F:37])([F:36])[F:25])=[CH:29][CH:30]=3)[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[N:5]=2)=[CH:16][CH:17]=1

Participants

9

Reactant 4

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)5×HCID 69573p-(Trifluoromethoxy)benzaldehydeHCID 86661475HCID 86661475, compound

Product 1

HCID 66679419HCID 66679419, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent2×HCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 6-chloro-N-(4-chlorophenyl)-2-phenylpyrimidin-4-amine (XXIII) (161.87 mg, 0.51 mmol) in 1,4-dioxane (5 mL) was treated with hydrazine monohydrate (120 uL, 2.47 mmol) and stirred at room temperature for 1 hour. The reaction was then stirred at 40° C. for 135 minutes and treated with additional hydrazine monohydrate (300 uL, 6.18 mmol). Stirred with heat for 30 minutes and treated with additional hydrazine monohydrate (700 uL, 14.43 mmol). Stirred with heat for 30 minutes and treated with additional hydrazine monohydrate (1.5 mL, 30.9 mmol) and stirred for 15 minutes. Treated with hydrazine monohydrate (500 uL, 10.3 mmol, new bottle) and stirred overnight at ˜50° C. The reaction was cooled and partitioned between water and dichloromethane. The organic layer was concentrated on a rotary evaporator to yield a film (229.26 mg). The film (assumed 0.51 mmol) was treated with absolute ethanol (5 mL). The mixture was treated with a solution of with 4-trifluoromethoxybenzaldehyde (194.7 mg, 1.02 mmol) in absolute ethanol (3 mL). The mixture was treated with 3 drops of acetic acid and stirred at room temperature for 3 hours. The reaction was treated with water (35 mL) and stirred for 30 minutes. The aqueous solution was extracted 3 times with ethyl acetate. The combined organics was dried over magnesium sulfate, filtered and concentrated to yield a film. The film was taken up in chloroform and loaded onto 100 g of silica gel. The silica gel was eluted with ethyl acetate/hexanes (10%, 15%, 20%, 30%). The appropriate fractions were concentrated to yield N-(4-chlorophenyl)-2-phenyl-6-(2-(4-(trifluoromethoxy)benzylidene)hydrazinyl)pyrimidin-4-amine (Example 46) as a film (233.6 mg). ESI/MS 483.6, 485.9 (M+H), 482.0, 484.0 (M−H).

Workup

  1. stirringThe reaction was then stirred at 40° C. for 135 minutes
  2. stirringStirred
  3. temperaturewith heat for 30 minutes
  4. stirringStirred
  5. temperaturewith heat for 30 minutes
  6. stirringstirred for 15 minutes
  7. stirringstirred overnight at ˜50° C
  8. temperatureThe reaction was cooled
  9. custompartitioned between water and dichloromethane
  10. concentrationThe organic layer was concentrated on a rotary evaporator
  11. customto yield a film (229.26 mg)
  12. stirringstirred at room temperature for 3 hours
  13. stirringstirred for 30 minutes
  14. extractionThe aqueous solution was extracted 3 times with ethyl acetate
  15. dry with materialThe combined organics was dried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customto yield a film
  19. washThe silica gel was eluted with ethyl acetate/hexanes (10%, 15%, 20%, 30%)
  20. concentrationThe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-23668addd354409bb982f89ca7a18989
Source dataset
uspto-grants-2014_07
Patent number
US08785630B2

Reaction notes

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