Phosphorus oxychloride → 4-chloro-2-pyridin-4-ylquinazoline

HRID 2357879Notes

Reaction equation

HRID 2357879 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[NH:16][C:15](=O)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:19].O=P(Cl)(Cl)Cl>>[Cl:19][C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[N:16]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 1354126684-Hydroxy-2-(pyridin-4-yl)quinazoline, 4-(4-Hydroxyquinazolin-2-yl)pyridine

Product 1

HCID 47368494-chloro-2-pyridin-4-ylquinazolineYield 60%

Procedure

2-Pyridin-4-ylquinazolin-4(3H)-one (1 mmol) and PCl5 (1.5 mmol) were suspended in POCl3 (12 mmol). The reaction mixture was brought to reflux over 4 h. The solvent was concentrated to dryness and the amorphous residue was partitioned with ethyl acetate and ice water. The aqueous layer was extracted with additional ethyl acetate and the combined organic layers were washed with 10% Na2CO3 and brine and dried over magnesium sulfate. The filtrate was concentrated and dried in vacuo to afford the desired product as a brown solid. (60% yield). 1H NMR (400 MHz, d6-DMSO): δ 8.84 (d, 2H), 8.36 (d, 2H), 8.12 (m, 2H), 7.88 (m, 2H). MS (EI) for C13H8ClN3: 242 (MH+).

Workup

  1. temperatureto reflux over 4 h
  2. concentrationThe solvent was concentrated to dryness
  3. customthe amorphous residue was partitioned with ethyl acetate and ice water
  4. extractionThe aqueous layer was extracted with additional ethyl acetate
  5. washthe combined organic layers were washed with 10% Na2CO3 and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationThe filtrate was concentrated
  8. customdried in vacuo

Sources & evidence

ORD record
ord-6062944d236343fcb33cf0f02c407193
Source dataset
uspto-grants-2010_07
Patent number
US07763627B2

Reaction notes

Loading…