HCID 58065805, compound → HCID 56643894, compound

HRID 2370974Notes

Reaction equation

HRID 2370974 reaction equation
Cl.Cl[C:3]1[N:8]=[C:7]([NH:9][CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[C:6]([F:20])=[CH:5][N:4]=1.[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]4[CH2:37][CH2:36]4)=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:38])=[C:26]([F:39])[CH:25]=2)[CH2:23][CH2:22]1>CC(O)C>[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH:35]4[CH2:37][CH2:36]4)=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH:38][C:3]3[N:8]=[C:7]([NH:9][CH:10]4[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]4)[C:6]([F:20])=[CH:5][N:4]=3)=[C:26]([F:39])[CH:25]=2)[CH2:23][CH2:22]1

Participants

4

Reactant 2

HCID 58065805HCID 58065805, compoundHCID 86653878HCID 86653878, compound

Product 1

HCID 56643894HCID 56643894, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (256 mg, 0.791 mmol, 1 equiv), 4-cyclopropyl-5-(5-cyclopropyl-1H-tetrazol-1-yl)-2-fluorobenzenamine (205 mg, 0.791 mmol, 1 equiv), and PTSA monohydrate (120 mg, 0.633 mmol, 0.8 equiv) in IPA (8 mL) were heated to 70° C. for 8 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 2×, dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by trituration from EtOAc:hexane to give compound N2-(4-cyclopropyl-5-(5-cyclopropyl-1H-tetrazol-1-yl)-2-fluorophenyl)-5-fluoro-N4-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine (276 mg, 68%) as a solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe crude mixture was concentrated to dryness
  3. customThe layers were separated
  4. washThe organic layer was washed with 1N NaOH 2×
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by trituration from EtOAc

Sources & evidence

ORD record
ord-b6faf8ddbe7349e09aa5b93d34451b45
Source dataset
uspto-grants-2014_04
Patent number
US08710223B2

Reaction notes

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