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

HRID 1386211Notes

Reaction equation

HRID 1386211 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 NaHCO3 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, 470%), mp (MeOH) 211-213° C. 1H NMR (DMSO) 5 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 NaHCO3 and EtOAc
  5. extractionThe organic extract

Sources & evidence

ORD record
ord-fbb326a51e89497ba71e658dce71da07
Source dataset
uspto-grants-2001_07
Patent number
US06265410B1

Reaction notes

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