Hydrochloric Acid → HCID 90410870, compound

HRID 573985Notes

Reaction equation

HRID 573985 reaction equation
Cl.C([N:9]1[CH:13]=[C:12]([C:14]2[CH:15]=[C:16]([NH:22][C:23]3[N:28]=[C:27]([NH:29][C@H:30]([C:32]4[CH:37]=[CH:36][C:35]([F:38])=[CH:34][N:33]=4)[CH3:31])[C:26]([CH3:39])=[CH:25][N:24]=3)[C:17]([O:20][CH3:21])=[N:18][CH:19]=2)[CH:11]=[N:10]1)C1C=CC=CC=1>[Pd].[OH-].[OH-].[Pd+2].CO.O1CCCC1>[F:38][C:35]1[CH:36]=[CH:37][C:32]([C@@H:30]([NH:29][C:27]2[C:26]([CH3:39])=[CH:25][N:24]=[C:23]([NH:22][C:16]3[C:17]([O:20][CH3:21])=[N:18][CH:19]=[C:14]([C:12]4[CH:11]=[N:10][NH:9][CH:13]=4)[CH:15]=3)[N:28]=2)[CH3:31])=[N:33][CH:34]=1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid3×HCID 90410465HCID 90410465, compound

Product 1

HCID 90410870HCID 90410870, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 9942167Palladium hydroxideCatalyst2×HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

5N Aqueous hydrochloric acid solution (0.126 mL, 0.63 mmol) and 20% palladium hydroxide on carbon (0.07 g, 0.50 mmol) were added to a solution of (S)—N2-(5-(1-benzyl-1H-pyrazol-4-yl)-2-methoxypyridin-3-yl)-N4-(1-(5-fluoropyridin-2-yl)ethyl)-5-methylpyrimidine-2,4-diamine (Preparation 9a, 0.214 g, 0.42 mmol) in a 1:1 mixture of methanol/tetrahydrofuran (4 mL) and the reaction mixture was stirred at 50° C. overnight under a hydrogen atmosphere. Further 5N aqueous hydrochloric acid solution (0.126 mL, 0.63 mmol) and palladium catalyst (0.07 g) were then added and the mixture was stirred overnight under a hydrogen atmosphere. The mixture was then filtered through diatomaceous earth (Celite®) and the filter cake was washed with methanol. The combined filtrate and washings were evaporated and a 1:1 mixture of methanol/tetrahydrofuran (4 mL) was added to the residue. 5N aqueous hydrochloric acid solution (0.126 mL, 0.63 mmol) and 20% palladium hydroxide on carbon (0.07 g, 0.50 mmol) were then added to the resulting solution and the reaction mixture was stirred at 50° C. overnight under a hydrogen atmosphere. The mixture was then filtered through Celite® and the filter cake was washed with methanol. The combined filtrate and washings were evaporated to give the title compound (0.166 g, 70%) as a white foam that was used in the next synthetic step without further purification.

Workup

  1. stirringthe mixture was stirred overnight under a hydrogen atmosphere
  2. filtrationThe mixture was then filtered through diatomaceous earth (Celite®)
  3. washthe filter cake was washed with methanol
  4. customThe combined filtrate and washings were evaporated
  5. additiona 1:1 mixture of methanol/tetrahydrofuran (4 mL)
  6. additionwas added to the residue
  7. stirringthe reaction mixture was stirred at 50° C. overnight under a hydrogen atmosphere
  8. filtrationThe mixture was then filtered through Celite®
  9. washthe filter cake was washed with methanol
  10. customThe combined filtrate and washings were evaporated

Sources & evidence

ORD record
ord-db58e3c342264a0a844c49c7c762ed41
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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