Water → 2-Hydrazino-4-(2-pyridyl)pyrimidine

HRID 2074978Notes

Reaction equation

HRID 2074978 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][NH:10][C:9](=O)[N:8]=1.O.[OH-].[Na+].O.[NH2:18][NH2:19]>P(Cl)(Cl)(Cl)=O.C(Cl)Cl.CO>[NH:18]([C:9]1[N:8]=[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH:12]=[CH:11][N:10]=1)[NH2:19]

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 178517490HCID 178517490, compound

Product 1

HCID 221748552-Hydrazino-4-(2-pyridyl)pyrimidineYield 30%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-amino-4-(2-pyridyl)pyrimidine (10.10 g, 58.66 mmol) in 5% aqueous sulfuric acid (200 mL) was added sodium nitrate (20.24 g, 293.3 mmol) portionwise over 10 min. The solution was stirred at room temperature for 2 h and was then adjusted to pH 10 by addition of 6N aq. NaOH. The resulting mixture was then extracted with 30% i-PrOH in CHCl3 (10×300 mL), and the combined organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was triturated with hexanes and collected by vacuum filtration to afford 6.89 g of 4-(2-pyridyl)pyrimid-2-one (68%) as a beige solid. A mixture of 4-(2-pyridyl)pyrimid-2-one (6.89 g, 39.8 mmol) in phosphorus oxychloride (30 mL) was heated at 110° C. for 90 min in a sealed tube. The dark brown solution was then cooled to room temperature and poured over cracked ice and water (500 mL). The mixture was vigorously stirred at 0° C. for 1 h, and was then adjusted to pH 14 with 6 N aq NaOH. The mixture was extracted with CH2Cl2 (2×300 mL), and the combined organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. To a solution of the residue in CH2Cl2 (10 mL) and MeOH (30 mL) was added hydrazine monohydrate (7.0 mL, 144.2 mmol), and the solution was stirred for 16 h at which time a white precipitate was observed. This solid was collected by vacuum filtration, washed with water, and dried in vacuo to provide 2.20 g of the title compound (30%) as an off-white solid. MH+188.

Workup

  1. temperatureThe dark brown solution was then cooled to room temperature
  2. extractionThe mixture was extracted with CH2Cl2 (2×300 mL)
  3. dry with materialthe combined organic phase was dried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. stirringthe solution was stirred for 16 h at which time a white precipitate
  6. filtrationThis solid was collected by vacuum filtration
  7. washwashed with water
  8. customdried in vacuo

Sources & evidence

ORD record
ord-4955cbe5f7e741bda433ac8017a3dc24
Source dataset
uspto-grants-2011_04
Patent number
US07919528B2

Reaction notes

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