Acetic Acid → [5-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-urea

HRID 38361

Reaction equation

HRID 38361 reaction equation
[NH2:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.C(O)(=O)C.[O-:26][C:27]#[N:28].[Na+]>O>[NH2:14][C:11]1[N:10]=[C:9]([NH2:15])[C:8]([O:7][C:6]2[C:5]([CH:17]([CH3:19])[CH3:18])=[CH:4][C:3]([O:20][CH3:21])=[C:2]([NH:1][C:27]([NH2:28])=[O:26])[CH:16]=2)=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 517096Sodium CyanateHCID 595985735-(5-Amino-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine

Product 1

HCID 59598622[5-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-urea

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 5-(5-amino-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (314 mg, 1.09 mmol) suspended in water (3 mL) was added acetic acid (0.25 mL, 4.34 mmol). Once all solids had dissolved, sodium cyanate (71 mg, 1.09 mmol, dissolved in 1.5 mL water) was added dropwise. After 30 minutes, the reaction was concentrated and purified with silica gel column chromatography eluting with 92/8/0.1 dichloromethane/methanol/ammonium hydroxide to yield [5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-urea as an off-white solid (244 mg, 68%, M+H)+=333), which was converted to a hydrochloride salt:

Workup

  1. dissolutionOnce all solids had dissolved
  2. concentrationthe reaction was concentrated
  3. custompurified with silica gel column chromatography
  4. washeluting with 92/8/0.1 dichloromethane/methanol/ammonium hydroxide

Sources & evidence

ORD record
ord-b63bb08e569e49c29868a83b711d5656
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Linked notes

Loading…