Ethanol → Quinazoline hydrochloride

HRID 2182565Notes

Reaction equation

HRID 2182565 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13]C1C=CC(N[C:19]2[C:28]3[C:23](=[CH:24][C:25](O)=[C:26](OC)[CH:27]=3)[N:22]=[CH:21][N:20]=2)=C(F)C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C>C(Cl)Cl>[ClH:13].[N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:19]=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 702Ethanol2×HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 21186983Quinazoline hydrochlorideYield 150.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), triphenylphosphine (314 mg, 1.2 mmol) and 22-morpholinoethoxy)ethanol (97 mg, 0.56 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature, triphenylphosphine (105 mg, 0.4 mmol), 22-morpholinoethoxy)ethanol (49 mg, 0.28 mmol) and diethyl azodicarboxylate (70 mg, 0.4 mmol) were added. The mixture was stirred for 1 hour at ambient temperature and was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was triturated with ether, collected by filtration and dissolved in methylene chloride. 2M Ethereal hydrogen chloride (0.5 ml) was added and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(22-morpholinoethoxy)ethoxy)quinazoline hydrochloride (100 mg, 45%).

Workup

  1. custom(prepared
  2. stirringThe mixture was stirred for 1 hour at ambient temperature
  3. customwas purified
  4. additionby pouring directly onto a silica column
  5. washeluting with methylene chloride/acetonitrile/methanol (6/3/1)
  6. customThe purified product was triturated with ether
  7. filtrationcollected by filtration
  8. dissolutiondissolved in methylene chloride
  9. addition2M Ethereal hydrogen chloride (0.5 ml) was added
  10. filtrationthe resulting precipitate was collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-13654ef57e964e10beae5605fb790e7f
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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