Trifluoroacetic acid → 2-(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)phenyl)acetonitrile

HRID 445048Notes

Reaction equation

HRID 445048 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[N:14]=[C:13](OS(C2C(C)=CC(C)=CC=2C)(=O)=O)[C:12]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35][C:36]#[N:37])=[CH:31][CH:30]=2)=[C:11]([CH3:38])[N:10]=1.[CH2:39]([NH2:44])[CH2:40][CH2:41][CH2:42][CH3:43].[OH-].[Na+]>C(OCCCC)(=O)C.C(#N)C>[NH2:8][C:9]1[N:10]=[C:11]([CH3:38])[C:12]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([CH2:35][C:36]#[N:37])=[CH:33][CH:34]=2)=[C:13]([NH:44][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[N:14]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8060PentylamineHCID 14798Sodium HydroxideHCID 866334092-Amino-5-(4-(cyanomethyl)benzyl)-6-methylpyrimidin-4-yl 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 595906382-(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)phenyl)acetonitrile

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 31272Butyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Trifluoroacetic acid (27.4 g) was slowly added to a suspension of the product from step (iii) (105.0 g) and n-pentylamine (62.9 g) in butyl acetate (877.8 g) and the mixture was heated at 120° C. for 2 hours. The mixture was cooled to 20° C. and 4% aq. NaOH (997.5 g) was added to the mixture. The organic layer was separated, washed with water (997.5 g) and 10% aq. NH4Cl (997.5 g) respectively and the solvent evaporated under reduced pressure to afford a solid. The solid was dissolved in acetonitrile (221.1 g) at 50° C. and the solution was cooled to 42° C., seeded and stirred at this temperature for 1 hour. After the mixture was cooled to 5° C. and stirred at 5° C. for 1 hour, the resulting precipitate was collected by filtration, washed with acetonitrile (2×31.5 g) and dried under reduced pressure to give the subtitle compound as a solid, 52.0 g; 1H NMR DMSO-d6: δ 7.23 (d, 2H), 7.11 (d, 2H), 6.17 (t, 1H), 5.68 (s, 2H), 3.96 (s, 2H), 3.73 (s, 2H), 3.27-3.22 (m, 2H), 2.00 (s, 3H), 1.47-1.40 (m, 2H), 1.28-1.19 (m, 2H), 1.17-1.09 (m, 2H), 0.82 (t, 3H).

Workup

  1. temperatureThe mixture was cooled to 20° C.
  2. customThe organic layer was separated
  3. washwashed with water (997.5 g) and 10% aq. NH4Cl (997.5 g) respectively
  4. customthe solvent evaporated under reduced pressure
  5. customto afford a solid
  6. temperaturethe solution was cooled to 42° C.
  7. temperatureAfter the mixture was cooled to 5° C.
  8. stirringstirred at 5° C. for 1 hour
  9. filtrationthe resulting precipitate was collected by filtration
  10. washwashed with acetonitrile (2×31.5 g)
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-eaee21aa7f9f45e5b3ce64d99ecfeaa9
Source dataset
uspto-grants-2013_07
Patent number
US08476288B2

Reaction notes

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