Sodium Hydroxide → 5-Chloro-N2-[5-(dimethylphosphoryl)-2-methoxyphenyl]-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine

HRID 921304Notes

Reaction equation

HRID 921304 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:5]([Cl:21])=[CH:4][N:3]=1.[CH3:22][P:23]([C:26]1[CH:27]=[CH:28][C:29]([O:33][CH3:34])=[C:30]([CH:32]=1)[NH2:31])([CH3:25])=[O:24].[OH-].[Na+]>COCCO>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])=[N:7][C:2]([NH:31][C:30]2[CH:32]=[C:26]([P:23]([CH3:22])([CH3:25])=[O:24])[CH:27]=[CH:28][C:29]=2[O:33][CH3:34])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 597643782,5-dichloro-N-(2-((1-methylethyl)sulfonyl)phenyl)-4-pyrimidinamineHCID 670526575-(Dimethylphosphoryl)-2-methoxyaniline

Product 1

HCID 681573555-Chloro-N2-[5-(dimethylphosphoryl)-2-methoxyphenyl]-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamineYield 48.7%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2,5-dichloro-N-[2-(propan-2-ylsulfonyl)phenyl]pyrimidin-4-amine (as prepared in Example 17: 0.077 g, 0.22 mmol) in 1.5 mL of 2-methoxyethanol was added 5-(dimethylphosphoryl)-2-methoxyaniline (0.050 g, 0.21 mmol) as its hydrochloride salt. The mixture was heated in a sealed tube at 90° C. for 16 h. The mixture was basified with 1N NaOH solution, and extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution, dried with sodium sulfate, filtered and concentrated. The crude residue was purified by prep-HPLC to afford the final compound (52 mg, 48% yield). MS/ES+: m/z=509.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-912fce8834f74865bb627aa3ad7ef9da
Source dataset
uspto-grants-2016_03
Patent number
US09273077B2

Reaction notes

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