(5R)-1-(3-aminophenyl)-5-methyl-4-(trifluoroacetyl)-2-piperazinone → 2-{[5-fluoro-2-({3-[(5R)-5-methyl-2-oxo-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]amino}-N-(1-methylethyl)benzamide

HRID 1362891Notes

Reaction equation

HRID 1362891 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:20]=[CH:19][CH:18]=[CH:17][C:10]=2[C:11]([NH:13][CH:14]([CH3:16])[CH3:15])=[O:12])[C:5]([F:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:34][C@@H:33]([CH3:35])[N:32](C(=O)C(F)(F)F)[CH2:31][C:30]2=[O:42])[CH:26]=[CH:27][CH:28]=1>Cl>[F:21][C:5]1[C:6]([NH:8][C:9]2[CH:20]=[CH:19][CH:18]=[CH:17][C:10]=2[C:11]([NH:13][CH:14]([CH3:16])[CH3:15])=[O:12])=[N:7][C:2]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N:29]3[CH2:34][C@@H:33]([CH3:35])[NH:32][CH2:31][C:30]3=[O:42])[CH:24]=2)=[N:3][CH:4]=1

Participants

4

Reactant 2

HCID 57974166(5R)-1-(3-aminophenyl)-5-methyl-4-(trifluoroacetyl)-2-piperazinoneHCID 866218142-[(2-chloro-5-fluoro-4-pyrimidinyl)amino]-N-(1-methylethyl)benzamide

Product 1

HCID 669409842-{[5-fluoro-2-({3-[(5R)-5-methyl-2-oxo-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]amino}-N-(1-methylethyl)benzamideYield 55%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidCatalyst

Conditions

Temperature
95 °C

Procedure

To the suspension solution of 2-[(2-chloro-5-fluoro-4-pyrimidinyl)amino]-N-(1-methylethyl)benzamide (100 mg, 0.32 mmol) and (5R)-1-(3-aminophenyl)-5-methyl-4-(trifluoroacetyl)-2-piperazinone (147 mg, 0.48 mmol) was added 2 drops of 12N HCl. The reaction mixture was then sealed and heated in a 95° C. oil bath for 16 h. The reaction was followed by LC/MS. The reaction was evaporated to dryness. The residue was then dissolved in THF (10 mL) with LiOH (1.0 M solution 0.64 mL). The reaction mixture was heated at 50° C. for 3 h. Then the solvent was evaporated to dryness on high vacuum and the residue was loaded on silica gel column and eluted with 2.0 to 9.0% MeOH (with 0.1% NH4OH) in CH2Cl2. Oil was then recrystallized from hot EtOH to yield the pure title compound (84 mg, 55%). MS: M(C25H28FN7O2)=477.54 (M+H)+=478.

Workup

  1. customThe reaction mixture was then sealed
  2. customThe reaction was evaporated to dryness
  3. dissolutionThe residue was then dissolved in THF (10 mL) with LiOH (1.0 M solution 0.64 mL)
  4. temperatureThe reaction mixture was heated at 50° C. for 3 h
  5. customThen the solvent was evaporated to dryness on high vacuum
  6. washeluted with 2.0 to 9.0% MeOH (with 0.1% NH4OH) in CH2Cl2
  7. customOil was then recrystallized from hot EtOH

Sources & evidence

ORD record
ord-2d25b4f7e21d4186a04e9f877f6d3739
Source dataset
uspto-grants-2011_02
Patent number
US07884098B2

Reaction notes

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