Phosphorus oxychloride → 4-Chloro-7-fluoropyrido[2,3-d]pyrimidine

HRID 2256176Notes

Reaction equation

HRID 2256176 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=O)[NH:9][CH:8]=[N:7][C:6]=2[N:12]=1.O=P(Cl)(Cl)[Cl:15]>>[Cl:15][C:10]1[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[N:12][C:6]=2[N:7]=[CH:8][N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 135485944HCID 135485944, compound

Product 1

HCID 108213304-Chloro-7-fluoropyrido[2,3-d]pyrimidine

Procedure

A suspension of 7-fluoropyrido[2,3-d]pyrimid-4(3H)-one (0.20 g, 1.21 mmol) in POCl3 (10 mL) is heated under reflux for 2 h. The volatiles are then removed under reduced pressure, and the residue is partitioned between aqueous NaHCl and EtOAc. The organic extract is worked up to give crude 4-chloro-7-fluoropyrido[2,3-d]pyrimidine, which is used directly in the next reaction. A solution of this product (0.20 g, 1.09 mmol) and 3-bromoaniline (0.23 mL, 2.18 mmol) in propan-2-ol (1.0 mL) and THF (10 mL) containing a trace of conc. HCl is stirred at 20° C. for 1 h, and then concentrated to dryness. The residue is dissolved in EtOAc, washed with aqueous NaHCO3, and worked up to give an oil, which is chromatographed on silica gel. Elution with EtOAc/petroleum ether (1:5) gives 3-bromoaniline, while EtoAc/petroleum ether (1:1) elutes 4-(3-bromoanilino)-7-fluoropyrido[2,3-d]pyrimidine (0.18 g, 47%), mp (MeOH) 211°-213° C. 1H NMR (DMSO) δ 10.18 (1H, brs), 9.17 (1H, t, J=8.6 Hz), 8.80 (1H, s), 8.17 (1H, t, J=1.8 Hz), 7.85 (1H, dt, Jd =7.6 Hz, Jt =1.8 Hz), 7.53 (1H, dd, J=8.6, 2.7 Hz), 7.41-7.34 (2H, m).

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 2 h
  3. customThe volatiles are then removed under reduced pressure
  4. customthe residue is partitioned between aqueous NaHCl and EtOAc
  5. extractionThe organic extract

Sources & evidence

ORD record
ord-2a1c6ac7a86e4eb7b8f3e0c48b6ed4c0
Source dataset
uspto-grants-1997_08
Patent number
US05654307

Reaction notes

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