Hydrochloric Acid → N2-[4-(Dimethylphosphoryl)-2-methoxyphenyl]-5-methyl-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine

HRID 1471967Notes

Reaction equation

HRID 1471967 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]([CH3:21])=[CH:4][N:3]=1.[CH3:22][P:23]([C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[C:28]([O:33][CH3:34])[CH:27]=1)([CH3:25])=[O:24].Cl>COCCO>[CH3:25][P:23]([C:26]1[CH:32]=[CH:31][C:29]([NH:30][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:5]([CH3:21])=[CH:4][N:3]=2)=[C:28]([O:33][CH3:34])[CH:27]=1)([CH3:22])=[O:24]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 597644732-chloro-N-(2-(isopropylsulfonyl)phenyl)-5-methylpyrimidin-4-amineHCID 67052699(4-Amino-3-methoxyphenyl)dimethylphosphine oxide

Product 1

HCID 68165221N2-[4-(Dimethylphosphoryl)-2-methoxyphenyl]-5-methyl-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamineYield 29%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-chloro-5-methyl-N-[2-(propan-2-ylsulfonyl)phenyl]-pyrimidin-4-amine (0.035 g, 0.11 mmol) in 1 mL of 2-methoxyethanol in a vial was added 4-(dimethylphosphoryl)-2-methyoxyaniline (0.020 g, 0.085 mmol) as the HCl salt. The vial was sealed and the reaction was heated at 90° C. for 16 h. The reaction was quenched with 1N NaOH solution and the solution extracted 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 silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford the desired compound (12 mg, 29% yield). MS/ES+: m/z=489.

Workup

  1. customThe vial was sealed
  2. customThe reaction was quenched with 1N NaOH solution
  3. extractionthe solution extracted ethyl acetate
  4. washwashed with saturated sodium chloride solution
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane)

Sources & evidence

ORD record
ord-292a673cb8e945f088692fcc13de9336
Source dataset
uspto-grants-2015_04
Patent number
US09012462B2

Reaction notes

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