Hydroxyamine hydrochloride → HCID 178490172, compound

HRID 1677324Notes

Reaction equation

HRID 1677324 reaction equation
Cl.[NH2:2][OH:3].C(=O)([O-])O.[Na+].[NH2:9][C:10]1[N:15]=[C:14]([NH2:16])[C:13]([O:17][C:18]2[C:19]([CH:28]([CH3:30])[CH3:29])=[CH:20][C:21]([O:26][CH3:27])=[C:22]([CH:25]=2)[C:23]#[N:24])=[CH:12][N:11]=1>C(O)C.O>[NH2:9][C:10]1[N:15]=[C:14]([NH2:16])[C:13]([O:17][C:18]2[C:19]([CH:28]([CH3:30])[CH3:29])=[CH:20][C:21]([O:26][CH3:27])=[C:22]([CH:25]=2)[C:23]([NH:2][OH:3])=[NH:24])=[CH:12][N:11]=1

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochloride2×HCID 516892Sodium Bicarbonate2×HCID 445736915-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile

Product 1

HCID 178490172HCID 178490172, compoundYield 82.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

The benzamidination carried out in this step follows the procedure reported by Meyer et al., Synthesis 2003, 6, pp. 899-905. To a stirred mixture of hydroxylamine hydrochloride (0.099 g, 1.43 mmol) and sodium hydrogen carbonate (0.119 g, 1.42 mmol) in ethanol (1.4 ml) and water (0.3 ml) was added 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile (0.385 g, 1.29 mmol) and the mixture heated at reflux for 5 hours. A second portion of hydroxylamine hydrochloride (0.049 g, 0.71 mmol) and sodium hydrogen carbonate (0.060 g, 0.71 mmol) was added. After a further 2 hours the mixture was cooled, concentrated in vacuo, then diluted with water (10 ml) and extracted with ethyl acetate. The combined organic extracts were washed with brine then dried (MgSO4), filtered and concentrated in vacuo to yield 5-(2,4-diamino-pyrimidin-5-yloxy)-N-hydroxy-4-isopropyl-2-methoxy-benzamidine (355 mg) as a yellow foam. This material was used directly without further purification.

Workup

  1. customreported by Meyer et al., Synthesis 2003, 6
  2. temperaturethe mixture heated
  3. temperatureat reflux for 5 hours
  4. temperatureAfter a further 2 hours the mixture was cooled
  5. concentrationconcentrated in vacuo
  6. additiondiluted with water (10 ml)
  7. extractionextracted with ethyl acetate
  8. washThe combined organic extracts were washed with brine
  9. dry with materialthen dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2385e369de6b4365a77c5b59a1342d79
Source dataset
uspto-grants-2011_08
Patent number
US08008313B2

Reaction notes

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