Sodium Chloride → 4-(5-Methyl-3-phenylisoxazol-4-yl)pyrimidin-2-amine

HRID 2120853Notes

Reaction equation

HRID 2120853 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13](=O)[CH3:14].[CH3:16]OC(OC)N(C)C.[Na+].[Cl-].Cl.[NH2:27][C:28]([NH2:30])=[NH:29].C[O-].[Na+]>CO.C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[CH:14]=[CH:16][N:27]=[C:28]([NH2:30])[N:29]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 5742Guanidine HydrochlorideHCID 78373Dimethylformamide dimethyl acetalHCID 3185241-(5-Methyl-3-phenylisoxazol-4-yl)ethanoneHCID 10942334Sodium Methoxide

Product 1

HCID 27457214-(5-Methyl-3-phenylisoxazol-4-yl)pyrimidin-2-amineYield 41.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The above Compound 3 (17.7 g, 0.088 mol) and dimethylformamide dimethyl acetal (DMF.DMA) (160 g, 0.132 mol) were refluxed overnight. To the reaction mixture was added ethyl acetate and saturated aqueous NaCl. The organic phase was washed with saturated aqueous NaCl (twice) and dried (MgSO4). The organic solvent was removed under reduced pressure, and the crude product material was dissolved in 200 mL methanol. To the solution was added guanidine hydrochloride (10.5 g, 0.110 mol) in 100 mL methanol, followed by sodium methoxide (6.17 g, 0.114 mol) in 100 mL methanol. The reaction mixture was refluxed overnight and then was cooled to room temperature. The reaction solvent was concentrated to approximately 100 mL total volume, and the precipitated product was filtered. The filtration cake afforded the title compound (9.3 g). The overall yield for two steps was 46%.

Workup

  1. washThe organic phase was washed with saturated aqueous NaCl (twice) and
  2. dry with materialdried (MgSO4)
  3. customThe organic solvent was removed under reduced pressure
  4. dissolutionthe crude product material was dissolved in 200 mL methanol
  5. temperatureThe reaction mixture was refluxed overnight
  6. concentrationThe reaction solvent was concentrated to approximately 100 mL total volume
  7. filtrationthe precipitated product was filtered

Sources & evidence

ORD record
ord-ca28db4fc21346ada8cbdde9cfdd95fb
Source dataset
uspto-grants-2004_02
Patent number
US06693108B2

Reaction notes

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